IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ
Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism f...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Yunhao Tan [verfasserIn] Kenta Mosallanejad [verfasserIn] Qingxiu Zhang [verfasserIn] Stephen O’Brien [verfasserIn] Meghan Clements [verfasserIn] Stuart Perper [verfasserIn] Sarah Wilson [verfasserIn] Sudiksha Chaulagain [verfasserIn] Jing Wang [verfasserIn] Mary Abdalla [verfasserIn] Helen Al-Saidi [verfasserIn] Danyal Butt [verfasserIn] Anca Clabbers [verfasserIn] Kwasi Ofori [verfasserIn] Beth Dillon [verfasserIn] Bohdan Harvey [verfasserIn] John Memmott [verfasserIn] Christopher Negron [verfasserIn] David Winarta [verfasserIn] Catherine Tan [verfasserIn] Amlan Biswas [verfasserIn] Feng Dong [verfasserIn] Vanessa Morales-Tirado [verfasserIn] Xiaoqing Lu [verfasserIn] Gurminder Singh [verfasserIn] Michael White [verfasserIn] Shanna Ashley [verfasserIn] Heather Knight [verfasserIn] Susan Westmoreland [verfasserIn] Lucy Phillips [verfasserIn] Tracy Carr [verfasserIn] Lauren Reinke-Breen [verfasserIn] Rajeeva Singh [verfasserIn] Jianwen Xu [verfasserIn] Kan Wu [verfasserIn] Lisa Rinaldi [verfasserIn] Brian Stoll [verfasserIn] Yupeng David He [verfasserIn] Lisa Hazelwood [verfasserIn] Jozsef Karman [verfasserIn] Andrew McCluskey [verfasserIn] William Stine [verfasserIn] Ivan Correia [verfasserIn] Stephen Gauld [verfasserIn] Marc C. Levesque [verfasserIn] Geertruida Veldman [verfasserIn] Cedric Hubeau [verfasserIn] Timothy Radstake [verfasserIn] Ramkrishna Sadhukhan [verfasserIn] Edda Fiebiger [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2024 |
|---|
| Schlagwörter: |
|---|
| Übergeordnetes Werk: |
In: Frontiers in Immunology - Frontiers Media S.A., 2011, 15(2024) |
|---|---|
| Übergeordnetes Werk: |
volume:15 ; year:2024 |
| Links: |
|---|
| DOI / URN: |
10.3389/fimmu.2024.1293883 |
|---|
| Katalog-ID: |
DOAJ100351719 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | DOAJ100351719 | ||
| 003 | DE-627 | ||
| 005 | 20240414091755.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240414s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fimmu.2024.1293883 |2 doi | |
| 035 | |a (DE-627)DOAJ100351719 | ||
| 035 | |a (DE-599)DOAJ6fa4a13cb80640969f85235ea03fd692 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 050 | 0 | |a RC581-607 | |
| 100 | 0 | |a Yunhao Tan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFβ. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFβ signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFβ at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFβ-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis. | ||
| 650 | 4 | |a IL11 | |
| 650 | 4 | |a fibrosis | |
| 650 | 4 | |a drug target | |
| 650 | 4 | |a STAT3 | |
| 650 | 4 | |a ERK | |
| 650 | 4 | |a stromal cell | |
| 653 | 0 | |a Immunologic diseases. Allergy | |
| 700 | 0 | |a Kenta Mosallanejad |e verfasserin |4 aut | |
| 700 | 0 | |a Qingxiu Zhang |e verfasserin |4 aut | |
| 700 | 0 | |a Stephen O’Brien |e verfasserin |4 aut | |
| 700 | 0 | |a Meghan Clements |e verfasserin |4 aut | |
| 700 | 0 | |a Stuart Perper |e verfasserin |4 aut | |
| 700 | 0 | |a Sarah Wilson |e verfasserin |4 aut | |
| 700 | 0 | |a Sudiksha Chaulagain |e verfasserin |4 aut | |
| 700 | 0 | |a Jing Wang |e verfasserin |4 aut | |
| 700 | 0 | |a Mary Abdalla |e verfasserin |4 aut | |
| 700 | 0 | |a Helen Al-Saidi |e verfasserin |4 aut | |
| 700 | 0 | |a Danyal Butt |e verfasserin |4 aut | |
| 700 | 0 | |a Anca Clabbers |e verfasserin |4 aut | |
| 700 | 0 | |a Kwasi Ofori |e verfasserin |4 aut | |
| 700 | 0 | |a Beth Dillon |e verfasserin |4 aut | |
| 700 | 0 | |a Bohdan Harvey |e verfasserin |4 aut | |
| 700 | 0 | |a John Memmott |e verfasserin |4 aut | |
| 700 | 0 | |a Christopher Negron |e verfasserin |4 aut | |
| 700 | 0 | |a David Winarta |e verfasserin |4 aut | |
| 700 | 0 | |a Catherine Tan |e verfasserin |4 aut | |
| 700 | 0 | |a Amlan Biswas |e verfasserin |4 aut | |
| 700 | 0 | |a Feng Dong |e verfasserin |4 aut | |
| 700 | 0 | |a Vanessa Morales-Tirado |e verfasserin |4 aut | |
| 700 | 0 | |a Xiaoqing Lu |e verfasserin |4 aut | |
| 700 | 0 | |a Gurminder Singh |e verfasserin |4 aut | |
| 700 | 0 | |a Michael White |e verfasserin |4 aut | |
| 700 | 0 | |a Shanna Ashley |e verfasserin |4 aut | |
| 700 | 0 | |a Heather Knight |e verfasserin |4 aut | |
| 700 | 0 | |a Susan Westmoreland |e verfasserin |4 aut | |
| 700 | 0 | |a Lucy Phillips |e verfasserin |4 aut | |
| 700 | 0 | |a Tracy Carr |e verfasserin |4 aut | |
| 700 | 0 | |a Lauren Reinke-Breen |e verfasserin |4 aut | |
| 700 | 0 | |a Rajeeva Singh |e verfasserin |4 aut | |
| 700 | 0 | |a Jianwen Xu |e verfasserin |4 aut | |
| 700 | 0 | |a Kan Wu |e verfasserin |4 aut | |
| 700 | 0 | |a Lisa Rinaldi |e verfasserin |4 aut | |
| 700 | 0 | |a Brian Stoll |e verfasserin |4 aut | |
| 700 | 0 | |a Yupeng David He |e verfasserin |4 aut | |
| 700 | 0 | |a Lisa Hazelwood |e verfasserin |4 aut | |
| 700 | 0 | |a Jozsef Karman |e verfasserin |4 aut | |
| 700 | 0 | |a Andrew McCluskey |e verfasserin |4 aut | |
| 700 | 0 | |a William Stine |e verfasserin |4 aut | |
| 700 | 0 | |a Ivan Correia |e verfasserin |4 aut | |
| 700 | 0 | |a Stephen Gauld |e verfasserin |4 aut | |
| 700 | 0 | |a Marc C. Levesque |e verfasserin |4 aut | |
| 700 | 0 | |a Geertruida Veldman |e verfasserin |4 aut | |
| 700 | 0 | |a Cedric Hubeau |e verfasserin |4 aut | |
| 700 | 0 | |a Timothy Radstake |e verfasserin |4 aut | |
| 700 | 0 | |a Ramkrishna Sadhukhan |e verfasserin |4 aut | |
| 700 | 0 | |a Edda Fiebiger |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i In |t Frontiers in Immunology |d Frontiers Media S.A., 2011 |g 15(2024) |w (DE-627)657998354 |w (DE-600)2606827-8 |x 16643224 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2024 |
| 856 | 4 | 0 | |u https://doi.org/10.3389/fimmu.2024.1293883 |z kostenfrei |
| 856 | 4 | 0 | |u https://doaj.org/article/6fa4a13cb80640969f85235ea03fd692 |z kostenfrei |
| 856 | 4 | 0 | |u https://www.frontiersin.org/articles/10.3389/fimmu.2024.1293883/full |z kostenfrei |
| 856 | 4 | 2 | |u https://doaj.org/toc/1664-3224 |y Journal toc |z kostenfrei |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_DOAJ | ||
| 912 | |a GBV_ILN_11 | ||
| 912 | |a GBV_ILN_20 | ||
| 912 | |a GBV_ILN_22 | ||
| 912 | |a GBV_ILN_23 | ||
| 912 | |a GBV_ILN_24 | ||
| 912 | |a GBV_ILN_39 | ||
| 912 | |a GBV_ILN_40 | ||
| 912 | |a GBV_ILN_60 | ||
| 912 | |a GBV_ILN_62 | ||
| 912 | |a GBV_ILN_63 | ||
| 912 | |a GBV_ILN_65 | ||
| 912 | |a GBV_ILN_69 | ||
| 912 | |a GBV_ILN_73 | ||
| 912 | |a GBV_ILN_74 | ||
| 912 | |a GBV_ILN_95 | ||
| 912 | |a GBV_ILN_105 | ||
| 912 | |a GBV_ILN_110 | ||
| 912 | |a GBV_ILN_151 | ||
| 912 | |a GBV_ILN_161 | ||
| 912 | |a GBV_ILN_170 | ||
| 912 | |a GBV_ILN_206 | ||
| 912 | |a GBV_ILN_213 | ||
| 912 | |a GBV_ILN_230 | ||
| 912 | |a GBV_ILN_285 | ||
| 912 | |a GBV_ILN_293 | ||
| 912 | |a GBV_ILN_602 | ||
| 912 | |a GBV_ILN_2003 | ||
| 912 | |a GBV_ILN_2014 | ||
| 912 | |a GBV_ILN_4012 | ||
| 912 | |a GBV_ILN_4037 | ||
| 912 | |a GBV_ILN_4112 | ||
| 912 | |a GBV_ILN_4125 | ||
| 912 | |a GBV_ILN_4126 | ||
| 912 | |a GBV_ILN_4249 | ||
| 912 | |a GBV_ILN_4305 | ||
| 912 | |a GBV_ILN_4306 | ||
| 912 | |a GBV_ILN_4307 | ||
| 912 | |a GBV_ILN_4313 | ||
| 912 | |a GBV_ILN_4322 | ||
| 912 | |a GBV_ILN_4323 | ||
| 912 | |a GBV_ILN_4324 | ||
| 912 | |a GBV_ILN_4325 | ||
| 912 | |a GBV_ILN_4338 | ||
| 912 | |a GBV_ILN_4367 | ||
| 912 | |a GBV_ILN_4700 | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2024 | ||
| author_variant |
y t yt k m km q z qz s o so m c mc s p sp s w sw s c sc j w jw m a ma h a s has d b db a c ac k o ko b d bd b h bh j m jm c n cn d w dw c t ct a b ab f d fd v m t vmt x l xl g s gs m w mw s a sa h k hk s w sw l p lp t c tc l r b lrb r s rs j x jx k w kw l r lr b s bs y d h ydh l h lh j k jk a m am w s ws i c ic s g sg m c l mcl g v gv c h ch t r tr r s rs e f ef |
|---|---|
| matchkey_str |
article:16643224:2024----::l1eitdtoaclatvtomyobteatreuaoopoirtc |
| hierarchy_sort_str |
2024 |
| callnumber-subject-code |
RC |
| publishDate |
2024 |
| allfields |
10.3389/fimmu.2024.1293883 doi (DE-627)DOAJ100351719 (DE-599)DOAJ6fa4a13cb80640969f85235ea03fd692 DE-627 ger DE-627 rakwb eng RC581-607 Yunhao Tan verfasserin aut IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFβ. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFβ signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFβ at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFβ-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis. IL11 fibrosis drug target STAT3 ERK stromal cell Immunologic diseases. Allergy Kenta Mosallanejad verfasserin aut Qingxiu Zhang verfasserin aut Stephen O’Brien verfasserin aut Meghan Clements verfasserin aut Stuart Perper verfasserin aut Sarah Wilson verfasserin aut Sudiksha Chaulagain verfasserin aut Jing Wang verfasserin aut Mary Abdalla verfasserin aut Helen Al-Saidi verfasserin aut Danyal Butt verfasserin aut Anca Clabbers verfasserin aut Kwasi Ofori verfasserin aut Beth Dillon verfasserin aut Bohdan Harvey verfasserin aut John Memmott verfasserin aut Christopher Negron verfasserin aut David Winarta verfasserin aut Catherine Tan verfasserin aut Amlan Biswas verfasserin aut Feng Dong verfasserin aut Vanessa Morales-Tirado verfasserin aut Xiaoqing Lu verfasserin aut Gurminder Singh verfasserin aut Michael White verfasserin aut Shanna Ashley verfasserin aut Heather Knight verfasserin aut Susan Westmoreland verfasserin aut Lucy Phillips verfasserin aut Tracy Carr verfasserin aut Lauren Reinke-Breen verfasserin aut Rajeeva Singh verfasserin aut Jianwen Xu verfasserin aut Kan Wu verfasserin aut Lisa Rinaldi verfasserin aut Brian Stoll verfasserin aut Yupeng David He verfasserin aut Lisa Hazelwood verfasserin aut Jozsef Karman verfasserin aut Andrew McCluskey verfasserin aut William Stine verfasserin aut Ivan Correia verfasserin aut Stephen Gauld verfasserin aut Marc C. Levesque verfasserin aut Geertruida Veldman verfasserin aut Cedric Hubeau verfasserin aut Timothy Radstake verfasserin aut Ramkrishna Sadhukhan verfasserin aut Edda Fiebiger verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 15(2024) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:15 year:2024 https://doi.org/10.3389/fimmu.2024.1293883 kostenfrei https://doaj.org/article/6fa4a13cb80640969f85235ea03fd692 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2024.1293883/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2024 |
| spelling |
10.3389/fimmu.2024.1293883 doi (DE-627)DOAJ100351719 (DE-599)DOAJ6fa4a13cb80640969f85235ea03fd692 DE-627 ger DE-627 rakwb eng RC581-607 Yunhao Tan verfasserin aut IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFβ. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFβ signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFβ at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFβ-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis. IL11 fibrosis drug target STAT3 ERK stromal cell Immunologic diseases. Allergy Kenta Mosallanejad verfasserin aut Qingxiu Zhang verfasserin aut Stephen O’Brien verfasserin aut Meghan Clements verfasserin aut Stuart Perper verfasserin aut Sarah Wilson verfasserin aut Sudiksha Chaulagain verfasserin aut Jing Wang verfasserin aut Mary Abdalla verfasserin aut Helen Al-Saidi verfasserin aut Danyal Butt verfasserin aut Anca Clabbers verfasserin aut Kwasi Ofori verfasserin aut Beth Dillon verfasserin aut Bohdan Harvey verfasserin aut John Memmott verfasserin aut Christopher Negron verfasserin aut David Winarta verfasserin aut Catherine Tan verfasserin aut Amlan Biswas verfasserin aut Feng Dong verfasserin aut Vanessa Morales-Tirado verfasserin aut Xiaoqing Lu verfasserin aut Gurminder Singh verfasserin aut Michael White verfasserin aut Shanna Ashley verfasserin aut Heather Knight verfasserin aut Susan Westmoreland verfasserin aut Lucy Phillips verfasserin aut Tracy Carr verfasserin aut Lauren Reinke-Breen verfasserin aut Rajeeva Singh verfasserin aut Jianwen Xu verfasserin aut Kan Wu verfasserin aut Lisa Rinaldi verfasserin aut Brian Stoll verfasserin aut Yupeng David He verfasserin aut Lisa Hazelwood verfasserin aut Jozsef Karman verfasserin aut Andrew McCluskey verfasserin aut William Stine verfasserin aut Ivan Correia verfasserin aut Stephen Gauld verfasserin aut Marc C. Levesque verfasserin aut Geertruida Veldman verfasserin aut Cedric Hubeau verfasserin aut Timothy Radstake verfasserin aut Ramkrishna Sadhukhan verfasserin aut Edda Fiebiger verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 15(2024) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:15 year:2024 https://doi.org/10.3389/fimmu.2024.1293883 kostenfrei https://doaj.org/article/6fa4a13cb80640969f85235ea03fd692 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2024.1293883/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2024 |
| allfields_unstemmed |
10.3389/fimmu.2024.1293883 doi (DE-627)DOAJ100351719 (DE-599)DOAJ6fa4a13cb80640969f85235ea03fd692 DE-627 ger DE-627 rakwb eng RC581-607 Yunhao Tan verfasserin aut IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFβ. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFβ signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFβ at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFβ-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis. IL11 fibrosis drug target STAT3 ERK stromal cell Immunologic diseases. Allergy Kenta Mosallanejad verfasserin aut Qingxiu Zhang verfasserin aut Stephen O’Brien verfasserin aut Meghan Clements verfasserin aut Stuart Perper verfasserin aut Sarah Wilson verfasserin aut Sudiksha Chaulagain verfasserin aut Jing Wang verfasserin aut Mary Abdalla verfasserin aut Helen Al-Saidi verfasserin aut Danyal Butt verfasserin aut Anca Clabbers verfasserin aut Kwasi Ofori verfasserin aut Beth Dillon verfasserin aut Bohdan Harvey verfasserin aut John Memmott verfasserin aut Christopher Negron verfasserin aut David Winarta verfasserin aut Catherine Tan verfasserin aut Amlan Biswas verfasserin aut Feng Dong verfasserin aut Vanessa Morales-Tirado verfasserin aut Xiaoqing Lu verfasserin aut Gurminder Singh verfasserin aut Michael White verfasserin aut Shanna Ashley verfasserin aut Heather Knight verfasserin aut Susan Westmoreland verfasserin aut Lucy Phillips verfasserin aut Tracy Carr verfasserin aut Lauren Reinke-Breen verfasserin aut Rajeeva Singh verfasserin aut Jianwen Xu verfasserin aut Kan Wu verfasserin aut Lisa Rinaldi verfasserin aut Brian Stoll verfasserin aut Yupeng David He verfasserin aut Lisa Hazelwood verfasserin aut Jozsef Karman verfasserin aut Andrew McCluskey verfasserin aut William Stine verfasserin aut Ivan Correia verfasserin aut Stephen Gauld verfasserin aut Marc C. Levesque verfasserin aut Geertruida Veldman verfasserin aut Cedric Hubeau verfasserin aut Timothy Radstake verfasserin aut Ramkrishna Sadhukhan verfasserin aut Edda Fiebiger verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 15(2024) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:15 year:2024 https://doi.org/10.3389/fimmu.2024.1293883 kostenfrei https://doaj.org/article/6fa4a13cb80640969f85235ea03fd692 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2024.1293883/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2024 |
| allfieldsGer |
10.3389/fimmu.2024.1293883 doi (DE-627)DOAJ100351719 (DE-599)DOAJ6fa4a13cb80640969f85235ea03fd692 DE-627 ger DE-627 rakwb eng RC581-607 Yunhao Tan verfasserin aut IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFβ. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFβ signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFβ at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFβ-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis. IL11 fibrosis drug target STAT3 ERK stromal cell Immunologic diseases. Allergy Kenta Mosallanejad verfasserin aut Qingxiu Zhang verfasserin aut Stephen O’Brien verfasserin aut Meghan Clements verfasserin aut Stuart Perper verfasserin aut Sarah Wilson verfasserin aut Sudiksha Chaulagain verfasserin aut Jing Wang verfasserin aut Mary Abdalla verfasserin aut Helen Al-Saidi verfasserin aut Danyal Butt verfasserin aut Anca Clabbers verfasserin aut Kwasi Ofori verfasserin aut Beth Dillon verfasserin aut Bohdan Harvey verfasserin aut John Memmott verfasserin aut Christopher Negron verfasserin aut David Winarta verfasserin aut Catherine Tan verfasserin aut Amlan Biswas verfasserin aut Feng Dong verfasserin aut Vanessa Morales-Tirado verfasserin aut Xiaoqing Lu verfasserin aut Gurminder Singh verfasserin aut Michael White verfasserin aut Shanna Ashley verfasserin aut Heather Knight verfasserin aut Susan Westmoreland verfasserin aut Lucy Phillips verfasserin aut Tracy Carr verfasserin aut Lauren Reinke-Breen verfasserin aut Rajeeva Singh verfasserin aut Jianwen Xu verfasserin aut Kan Wu verfasserin aut Lisa Rinaldi verfasserin aut Brian Stoll verfasserin aut Yupeng David He verfasserin aut Lisa Hazelwood verfasserin aut Jozsef Karman verfasserin aut Andrew McCluskey verfasserin aut William Stine verfasserin aut Ivan Correia verfasserin aut Stephen Gauld verfasserin aut Marc C. Levesque verfasserin aut Geertruida Veldman verfasserin aut Cedric Hubeau verfasserin aut Timothy Radstake verfasserin aut Ramkrishna Sadhukhan verfasserin aut Edda Fiebiger verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 15(2024) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:15 year:2024 https://doi.org/10.3389/fimmu.2024.1293883 kostenfrei https://doaj.org/article/6fa4a13cb80640969f85235ea03fd692 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2024.1293883/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2024 |
| allfieldsSound |
10.3389/fimmu.2024.1293883 doi (DE-627)DOAJ100351719 (DE-599)DOAJ6fa4a13cb80640969f85235ea03fd692 DE-627 ger DE-627 rakwb eng RC581-607 Yunhao Tan verfasserin aut IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFβ. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFβ signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFβ at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFβ-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis. IL11 fibrosis drug target STAT3 ERK stromal cell Immunologic diseases. Allergy Kenta Mosallanejad verfasserin aut Qingxiu Zhang verfasserin aut Stephen O’Brien verfasserin aut Meghan Clements verfasserin aut Stuart Perper verfasserin aut Sarah Wilson verfasserin aut Sudiksha Chaulagain verfasserin aut Jing Wang verfasserin aut Mary Abdalla verfasserin aut Helen Al-Saidi verfasserin aut Danyal Butt verfasserin aut Anca Clabbers verfasserin aut Kwasi Ofori verfasserin aut Beth Dillon verfasserin aut Bohdan Harvey verfasserin aut John Memmott verfasserin aut Christopher Negron verfasserin aut David Winarta verfasserin aut Catherine Tan verfasserin aut Amlan Biswas verfasserin aut Feng Dong verfasserin aut Vanessa Morales-Tirado verfasserin aut Xiaoqing Lu verfasserin aut Gurminder Singh verfasserin aut Michael White verfasserin aut Shanna Ashley verfasserin aut Heather Knight verfasserin aut Susan Westmoreland verfasserin aut Lucy Phillips verfasserin aut Tracy Carr verfasserin aut Lauren Reinke-Breen verfasserin aut Rajeeva Singh verfasserin aut Jianwen Xu verfasserin aut Kan Wu verfasserin aut Lisa Rinaldi verfasserin aut Brian Stoll verfasserin aut Yupeng David He verfasserin aut Lisa Hazelwood verfasserin aut Jozsef Karman verfasserin aut Andrew McCluskey verfasserin aut William Stine verfasserin aut Ivan Correia verfasserin aut Stephen Gauld verfasserin aut Marc C. Levesque verfasserin aut Geertruida Veldman verfasserin aut Cedric Hubeau verfasserin aut Timothy Radstake verfasserin aut Ramkrishna Sadhukhan verfasserin aut Edda Fiebiger verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 15(2024) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:15 year:2024 https://doi.org/10.3389/fimmu.2024.1293883 kostenfrei https://doaj.org/article/6fa4a13cb80640969f85235ea03fd692 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2024.1293883/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2024 |
| language |
English |
| source |
In Frontiers in Immunology 15(2024) volume:15 year:2024 |
| sourceStr |
In Frontiers in Immunology 15(2024) volume:15 year:2024 |
| format_phy_str_mv |
Article |
| institution |
findex.gbv.de |
| topic_facet |
IL11 fibrosis drug target STAT3 ERK stromal cell Immunologic diseases. Allergy |
| isfreeaccess_bool |
true |
| container_title |
Frontiers in Immunology |
| authorswithroles_txt_mv |
Yunhao Tan @@aut@@ Kenta Mosallanejad @@aut@@ Qingxiu Zhang @@aut@@ Stephen O’Brien @@aut@@ Meghan Clements @@aut@@ Stuart Perper @@aut@@ Sarah Wilson @@aut@@ Sudiksha Chaulagain @@aut@@ Jing Wang @@aut@@ Mary Abdalla @@aut@@ Helen Al-Saidi @@aut@@ Danyal Butt @@aut@@ Anca Clabbers @@aut@@ Kwasi Ofori @@aut@@ Beth Dillon @@aut@@ Bohdan Harvey @@aut@@ John Memmott @@aut@@ Christopher Negron @@aut@@ David Winarta @@aut@@ Catherine Tan @@aut@@ Amlan Biswas @@aut@@ Feng Dong @@aut@@ Vanessa Morales-Tirado @@aut@@ Xiaoqing Lu @@aut@@ Gurminder Singh @@aut@@ Michael White @@aut@@ Shanna Ashley @@aut@@ Heather Knight @@aut@@ Susan Westmoreland @@aut@@ Lucy Phillips @@aut@@ Tracy Carr @@aut@@ Lauren Reinke-Breen @@aut@@ Rajeeva Singh @@aut@@ Jianwen Xu @@aut@@ Kan Wu @@aut@@ Lisa Rinaldi @@aut@@ Brian Stoll @@aut@@ Yupeng David He @@aut@@ Lisa Hazelwood @@aut@@ Jozsef Karman @@aut@@ Andrew McCluskey @@aut@@ William Stine @@aut@@ Ivan Correia @@aut@@ Stephen Gauld @@aut@@ Marc C. Levesque @@aut@@ Geertruida Veldman @@aut@@ Cedric Hubeau @@aut@@ Timothy Radstake @@aut@@ Ramkrishna Sadhukhan @@aut@@ Edda Fiebiger @@aut@@ |
| publishDateDaySort_date |
2024-01-01T00:00:00Z |
| hierarchy_top_id |
657998354 |
| id |
DOAJ100351719 |
| language_de |
englisch |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">DOAJ100351719</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240414091755.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">240414s2024 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.3389/fimmu.2024.1293883</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ100351719</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ6fa4a13cb80640969f85235ea03fd692</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC581-607</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Yunhao Tan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFβ. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFβ signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFβ at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFβ-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">IL11</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">fibrosis</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">drug target</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">STAT3</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">ERK</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">stromal cell</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Immunologic diseases. Allergy</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Kenta Mosallanejad</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Qingxiu Zhang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Stephen O’Brien</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Meghan Clements</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Stuart Perper</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sarah Wilson</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sudiksha Chaulagain</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jing Wang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mary Abdalla</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Helen Al-Saidi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Danyal Butt</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Anca Clabbers</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Kwasi Ofori</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Beth Dillon</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Bohdan Harvey</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">John Memmott</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Christopher Negron</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">David Winarta</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Catherine Tan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Amlan Biswas</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Feng Dong</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Vanessa Morales-Tirado</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xiaoqing Lu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Gurminder Singh</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Michael White</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Shanna Ashley</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Heather Knight</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Susan Westmoreland</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lucy Phillips</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Tracy Carr</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lauren Reinke-Breen</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rajeeva Singh</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jianwen Xu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Kan Wu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lisa Rinaldi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Brian Stoll</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yupeng David He</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lisa Hazelwood</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jozsef Karman</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Andrew McCluskey</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">William Stine</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ivan Correia</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Stephen Gauld</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Marc C. Levesque</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Geertruida Veldman</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Cedric Hubeau</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Timothy Radstake</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ramkrishna Sadhukhan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Edda Fiebiger</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Frontiers in Immunology</subfield><subfield code="d">Frontiers Media S.A., 2011</subfield><subfield code="g">15(2024)</subfield><subfield code="w">(DE-627)657998354</subfield><subfield code="w">(DE-600)2606827-8</subfield><subfield code="x">16643224</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:15</subfield><subfield code="g">year:2024</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.3389/fimmu.2024.1293883</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/6fa4a13cb80640969f85235ea03fd692</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://www.frontiersin.org/articles/10.3389/fimmu.2024.1293883/full</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/1664-3224</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">15</subfield><subfield code="j">2024</subfield></datafield></record></collection>
|
| callnumber-first |
R - Medicine |
| author |
Yunhao Tan |
| spellingShingle |
Yunhao Tan misc RC581-607 misc IL11 misc fibrosis misc drug target misc STAT3 misc ERK misc stromal cell misc Immunologic diseases. Allergy IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ |
| authorStr |
Yunhao Tan |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)657998354 |
| format |
electronic Article |
| delete_txt_mv |
keep |
| author_role |
aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut |
| collection |
DOAJ |
| remote_str |
true |
| callnumber-label |
RC581-607 |
| illustrated |
Not Illustrated |
| issn |
16643224 |
| topic_title |
RC581-607 IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ IL11 fibrosis drug target STAT3 ERK stromal cell |
| topic |
misc RC581-607 misc IL11 misc fibrosis misc drug target misc STAT3 misc ERK misc stromal cell misc Immunologic diseases. Allergy |
| topic_unstemmed |
misc RC581-607 misc IL11 misc fibrosis misc drug target misc STAT3 misc ERK misc stromal cell misc Immunologic diseases. Allergy |
| topic_browse |
misc RC581-607 misc IL11 misc fibrosis misc drug target misc STAT3 misc ERK misc stromal cell misc Immunologic diseases. Allergy |
| format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
cr |
| hierarchy_parent_title |
Frontiers in Immunology |
| hierarchy_parent_id |
657998354 |
| hierarchy_top_title |
Frontiers in Immunology |
| isfreeaccess_txt |
true |
| familylinks_str_mv |
(DE-627)657998354 (DE-600)2606827-8 |
| title |
IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ |
| ctrlnum |
(DE-627)DOAJ100351719 (DE-599)DOAJ6fa4a13cb80640969f85235ea03fd692 |
| title_full |
IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ |
| author_sort |
Yunhao Tan |
| journal |
Frontiers in Immunology |
| journalStr |
Frontiers in Immunology |
| callnumber-first-code |
R |
| lang_code |
eng |
| isOA_bool |
true |
| recordtype |
marc |
| publishDateSort |
2024 |
| contenttype_str_mv |
txt |
| author_browse |
Yunhao Tan Kenta Mosallanejad Qingxiu Zhang Stephen O’Brien Meghan Clements Stuart Perper Sarah Wilson Sudiksha Chaulagain Jing Wang Mary Abdalla Helen Al-Saidi Danyal Butt Anca Clabbers Kwasi Ofori Beth Dillon Bohdan Harvey John Memmott Christopher Negron David Winarta Catherine Tan Amlan Biswas Feng Dong Vanessa Morales-Tirado Xiaoqing Lu Gurminder Singh Michael White Shanna Ashley Heather Knight Susan Westmoreland Lucy Phillips Tracy Carr Lauren Reinke-Breen Rajeeva Singh Jianwen Xu Kan Wu Lisa Rinaldi Brian Stoll Yupeng David He Lisa Hazelwood Jozsef Karman Andrew McCluskey William Stine Ivan Correia Stephen Gauld Marc C. Levesque Geertruida Veldman Cedric Hubeau Timothy Radstake Ramkrishna Sadhukhan Edda Fiebiger |
| container_volume |
15 |
| class |
RC581-607 |
| format_se |
Elektronische Aufsätze |
| author-letter |
Yunhao Tan |
| doi_str_mv |
10.3389/fimmu.2024.1293883 |
| author2-role |
verfasserin |
| title_sort |
il11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of tgfβ |
| callnumber |
RC581-607 |
| title_auth |
IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ |
| abstract |
Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFβ. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFβ signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFβ at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFβ-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis. |
| abstractGer |
Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFβ. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFβ signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFβ at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFβ-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis. |
| abstract_unstemmed |
Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFβ. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFβ signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFβ at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFβ-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis. |
| collection_details |
GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 |
| title_short |
IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ |
| url |
https://doi.org/10.3389/fimmu.2024.1293883 https://doaj.org/article/6fa4a13cb80640969f85235ea03fd692 https://www.frontiersin.org/articles/10.3389/fimmu.2024.1293883/full https://doaj.org/toc/1664-3224 |
| remote_bool |
true |
| author2 |
Kenta Mosallanejad Qingxiu Zhang Stephen O’Brien Meghan Clements Stuart Perper Sarah Wilson Sudiksha Chaulagain Jing Wang Mary Abdalla Helen Al-Saidi Danyal Butt Anca Clabbers Kwasi Ofori Beth Dillon Bohdan Harvey John Memmott Christopher Negron David Winarta Catherine Tan Amlan Biswas Feng Dong Vanessa Morales-Tirado Xiaoqing Lu Gurminder Singh Michael White Shanna Ashley Heather Knight Susan Westmoreland Lucy Phillips Tracy Carr Lauren Reinke-Breen Rajeeva Singh Jianwen Xu Kan Wu Lisa Rinaldi Brian Stoll Yupeng David He Lisa Hazelwood Jozsef Karman Andrew McCluskey William Stine Ivan Correia Stephen Gauld Marc C. Levesque Geertruida Veldman Cedric Hubeau Timothy Radstake Ramkrishna Sadhukhan Edda Fiebiger |
| author2Str |
Kenta Mosallanejad Qingxiu Zhang Stephen O’Brien Meghan Clements Stuart Perper Sarah Wilson Sudiksha Chaulagain Jing Wang Mary Abdalla Helen Al-Saidi Danyal Butt Anca Clabbers Kwasi Ofori Beth Dillon Bohdan Harvey John Memmott Christopher Negron David Winarta Catherine Tan Amlan Biswas Feng Dong Vanessa Morales-Tirado Xiaoqing Lu Gurminder Singh Michael White Shanna Ashley Heather Knight Susan Westmoreland Lucy Phillips Tracy Carr Lauren Reinke-Breen Rajeeva Singh Jianwen Xu Kan Wu Lisa Rinaldi Brian Stoll Yupeng David He Lisa Hazelwood Jozsef Karman Andrew McCluskey William Stine Ivan Correia Stephen Gauld Marc C. Levesque Geertruida Veldman Cedric Hubeau Timothy Radstake Ramkrishna Sadhukhan Edda Fiebiger |
| ppnlink |
657998354 |
| callnumber-subject |
RC - Internal Medicine |
| mediatype_str_mv |
c |
| isOA_txt |
true |
| hochschulschrift_bool |
false |
| doi_str |
10.3389/fimmu.2024.1293883 |
| callnumber-a |
RC581-607 |
| up_date |
2024-07-03T14:12:31.142Z |
| _version_ |
1803567445995159552 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">DOAJ100351719</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240414091755.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">240414s2024 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.3389/fimmu.2024.1293883</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ100351719</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ6fa4a13cb80640969f85235ea03fd692</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC581-607</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Yunhao Tan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFβ. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFβ signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFβ at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFβ-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">IL11</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">fibrosis</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">drug target</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">STAT3</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">ERK</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">stromal cell</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Immunologic diseases. Allergy</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Kenta Mosallanejad</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Qingxiu Zhang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Stephen O’Brien</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Meghan Clements</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Stuart Perper</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sarah Wilson</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sudiksha Chaulagain</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jing Wang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mary Abdalla</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Helen Al-Saidi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Danyal Butt</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Anca Clabbers</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Kwasi Ofori</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Beth Dillon</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Bohdan Harvey</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">John Memmott</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Christopher Negron</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">David Winarta</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Catherine Tan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Amlan Biswas</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Feng Dong</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Vanessa Morales-Tirado</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xiaoqing Lu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Gurminder Singh</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Michael White</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Shanna Ashley</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Heather Knight</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Susan Westmoreland</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lucy Phillips</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Tracy Carr</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lauren Reinke-Breen</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rajeeva Singh</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jianwen Xu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Kan Wu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lisa Rinaldi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Brian Stoll</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yupeng David He</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lisa Hazelwood</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jozsef Karman</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Andrew McCluskey</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">William Stine</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ivan Correia</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Stephen Gauld</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Marc C. Levesque</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Geertruida Veldman</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Cedric Hubeau</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Timothy Radstake</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ramkrishna Sadhukhan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Edda Fiebiger</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Frontiers in Immunology</subfield><subfield code="d">Frontiers Media S.A., 2011</subfield><subfield code="g">15(2024)</subfield><subfield code="w">(DE-627)657998354</subfield><subfield code="w">(DE-600)2606827-8</subfield><subfield code="x">16643224</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:15</subfield><subfield code="g">year:2024</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.3389/fimmu.2024.1293883</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/6fa4a13cb80640969f85235ea03fd692</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://www.frontiersin.org/articles/10.3389/fimmu.2024.1293883/full</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/1664-3224</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">15</subfield><subfield code="j">2024</subfield></datafield></record></collection>
|
| score |
7.3998547 |