Tofacitinib Blocks Entheseal Lymphocyte Activation and Modulates MSC Adipogenesis, but Does Not Directly Affect Chondro- and Osteogenesis

Entheseal spinal inflammation and new bone formation with progressive ankylosis may occur in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). This study evaluated whether JAK inhibition with tofacitinib modulated the key disease associated cytokines, TNF and IL-17A, and whether tofacitinib...
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Autor*in:	Tobias Russell [verfasserIn] Hannah Rowe [verfasserIn] Charlie Bridgewood [verfasserIn] Richard J. Cuthbert [verfasserIn] Abdulla Watad [verfasserIn] Darren Newton [verfasserIn] Elena Jones [verfasserIn] Dennis McGonagle [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	tofacitinib JAK-STAT ankylosing spondylitis

Übergeordnetes Werk:	In: Immuno - MDPI AG, 2021, 1(2021), 4, Seite 545-557
Übergeordnetes Werk:	volume:1 ; year:2021 ; number:4 ; pages:545-557

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/immuno1040038

Katalog-ID:	DOAJ019186088

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520			\|a Entheseal spinal inflammation and new bone formation with progressive ankylosis may occur in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). This study evaluated whether JAK inhibition with tofacitinib modulated the key disease associated cytokines, TNF and IL-17A, and whether tofacitinib also modulated bone marrow stromal cell-derived mesenchymal stem cell (MSCs) function, including osteogenesis, since post inflammation new bone formation occurs under these conditions. Methods: Conventional entheseal derived αβ CD4+ and CD8+ T-cells were investigated following anti-CD3/CD28 bead stimulation to determine IL-17A and TNF levels in tofacitinib treated (1000 nM) peri-entheseal bone (PEB) and peripheral blood mononuclear cells (PBMC) using ELISA. Bone marrow stromal cell-derived mesenchymal stem cell (MSC) colony forming units (CFU-F) and multi-lineage potential were evaluated using tofacitinib (dosages ranging between 100, 500, 1000 and 10,000 nM). Results: Induced IL-17A and TNF cytokine production from both entheseal CD4+ T-cells and CD8+ T-cells was effectively inhibited by tofacitinib. Tofacitinib treatment did not impact on CFU-F potential or in vitro chondro- and osteogenesis. However, tofacitinib stimulation increased MSC adipogenic potential with greater Oil Red O stained areas. Conclusion: Inducible IL-17A and TNF production by healthy human entheseal CD4+ and CD8+ T-cells was robustly inhibited in vitro by tofacitinib. However, tofacitinib did not impact MSC osteogenesis, but stimulated in vitro MSC adipogenesis, the relevance of which needs further evaluation given that the adipocytes are associated with new bone formation in SpA.
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allfields	10.3390/immuno1040038 doi (DE-627)DOAJ019186088 (DE-599)DOAJ6e2ce4d124004ec2a411bdbe09605234 DE-627 ger DE-627 rakwb eng Tobias Russell verfasserin aut Tofacitinib Blocks Entheseal Lymphocyte Activation and Modulates MSC Adipogenesis, but Does Not Directly Affect Chondro- and Osteogenesis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Entheseal spinal inflammation and new bone formation with progressive ankylosis may occur in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). This study evaluated whether JAK inhibition with tofacitinib modulated the key disease associated cytokines, TNF and IL-17A, and whether tofacitinib also modulated bone marrow stromal cell-derived mesenchymal stem cell (MSCs) function, including osteogenesis, since post inflammation new bone formation occurs under these conditions. Methods: Conventional entheseal derived αβ CD4+ and CD8+ T-cells were investigated following anti-CD3/CD28 bead stimulation to determine IL-17A and TNF levels in tofacitinib treated (1000 nM) peri-entheseal bone (PEB) and peripheral blood mononuclear cells (PBMC) using ELISA. Bone marrow stromal cell-derived mesenchymal stem cell (MSC) colony forming units (CFU-F) and multi-lineage potential were evaluated using tofacitinib (dosages ranging between 100, 500, 1000 and 10,000 nM). Results: Induced IL-17A and TNF cytokine production from both entheseal CD4+ T-cells and CD8+ T-cells was effectively inhibited by tofacitinib. Tofacitinib treatment did not impact on CFU-F potential or in vitro chondro- and osteogenesis. However, tofacitinib stimulation increased MSC adipogenic potential with greater Oil Red O stained areas. Conclusion: Inducible IL-17A and TNF production by healthy human entheseal CD4+ and CD8+ T-cells was robustly inhibited in vitro by tofacitinib. However, tofacitinib did not impact MSC osteogenesis, but stimulated in vitro MSC adipogenesis, the relevance of which needs further evaluation given that the adipocytes are associated with new bone formation in SpA. tofacitinib JAK-STAT ankylosing spondylitis Medicine R Hannah Rowe verfasserin aut Charlie Bridgewood verfasserin aut Richard J. Cuthbert verfasserin aut Abdulla Watad verfasserin aut Darren Newton verfasserin aut Elena Jones verfasserin aut Dennis McGonagle verfasserin aut In Immuno MDPI AG, 2021 1(2021), 4, Seite 545-557 (DE-627)1768279497 26735601 nnns volume:1 year:2021 number:4 pages:545-557 https://doi.org/10.3390/immuno1040038 kostenfrei https://doaj.org/article/6e2ce4d124004ec2a411bdbe09605234 kostenfrei https://www.mdpi.com/2673-5601/1/4/38 kostenfrei https://doaj.org/toc/2673-5601 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_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 1 2021 4 545-557
spelling	10.3390/immuno1040038 doi (DE-627)DOAJ019186088 (DE-599)DOAJ6e2ce4d124004ec2a411bdbe09605234 DE-627 ger DE-627 rakwb eng Tobias Russell verfasserin aut Tofacitinib Blocks Entheseal Lymphocyte Activation and Modulates MSC Adipogenesis, but Does Not Directly Affect Chondro- and Osteogenesis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Entheseal spinal inflammation and new bone formation with progressive ankylosis may occur in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). This study evaluated whether JAK inhibition with tofacitinib modulated the key disease associated cytokines, TNF and IL-17A, and whether tofacitinib also modulated bone marrow stromal cell-derived mesenchymal stem cell (MSCs) function, including osteogenesis, since post inflammation new bone formation occurs under these conditions. Methods: Conventional entheseal derived αβ CD4+ and CD8+ T-cells were investigated following anti-CD3/CD28 bead stimulation to determine IL-17A and TNF levels in tofacitinib treated (1000 nM) peri-entheseal bone (PEB) and peripheral blood mononuclear cells (PBMC) using ELISA. Bone marrow stromal cell-derived mesenchymal stem cell (MSC) colony forming units (CFU-F) and multi-lineage potential were evaluated using tofacitinib (dosages ranging between 100, 500, 1000 and 10,000 nM). Results: Induced IL-17A and TNF cytokine production from both entheseal CD4+ T-cells and CD8+ T-cells was effectively inhibited by tofacitinib. Tofacitinib treatment did not impact on CFU-F potential or in vitro chondro- and osteogenesis. However, tofacitinib stimulation increased MSC adipogenic potential with greater Oil Red O stained areas. Conclusion: Inducible IL-17A and TNF production by healthy human entheseal CD4+ and CD8+ T-cells was robustly inhibited in vitro by tofacitinib. However, tofacitinib did not impact MSC osteogenesis, but stimulated in vitro MSC adipogenesis, the relevance of which needs further evaluation given that the adipocytes are associated with new bone formation in SpA. tofacitinib JAK-STAT ankylosing spondylitis Medicine R Hannah Rowe verfasserin aut Charlie Bridgewood verfasserin aut Richard J. Cuthbert verfasserin aut Abdulla Watad verfasserin aut Darren Newton verfasserin aut Elena Jones verfasserin aut Dennis McGonagle verfasserin aut In Immuno MDPI AG, 2021 1(2021), 4, Seite 545-557 (DE-627)1768279497 26735601 nnns volume:1 year:2021 number:4 pages:545-557 https://doi.org/10.3390/immuno1040038 kostenfrei https://doaj.org/article/6e2ce4d124004ec2a411bdbe09605234 kostenfrei https://www.mdpi.com/2673-5601/1/4/38 kostenfrei https://doaj.org/toc/2673-5601 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_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 1 2021 4 545-557
allfields_unstemmed	10.3390/immuno1040038 doi (DE-627)DOAJ019186088 (DE-599)DOAJ6e2ce4d124004ec2a411bdbe09605234 DE-627 ger DE-627 rakwb eng Tobias Russell verfasserin aut Tofacitinib Blocks Entheseal Lymphocyte Activation and Modulates MSC Adipogenesis, but Does Not Directly Affect Chondro- and Osteogenesis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Entheseal spinal inflammation and new bone formation with progressive ankylosis may occur in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). This study evaluated whether JAK inhibition with tofacitinib modulated the key disease associated cytokines, TNF and IL-17A, and whether tofacitinib also modulated bone marrow stromal cell-derived mesenchymal stem cell (MSCs) function, including osteogenesis, since post inflammation new bone formation occurs under these conditions. Methods: Conventional entheseal derived αβ CD4+ and CD8+ T-cells were investigated following anti-CD3/CD28 bead stimulation to determine IL-17A and TNF levels in tofacitinib treated (1000 nM) peri-entheseal bone (PEB) and peripheral blood mononuclear cells (PBMC) using ELISA. Bone marrow stromal cell-derived mesenchymal stem cell (MSC) colony forming units (CFU-F) and multi-lineage potential were evaluated using tofacitinib (dosages ranging between 100, 500, 1000 and 10,000 nM). Results: Induced IL-17A and TNF cytokine production from both entheseal CD4+ T-cells and CD8+ T-cells was effectively inhibited by tofacitinib. Tofacitinib treatment did not impact on CFU-F potential or in vitro chondro- and osteogenesis. However, tofacitinib stimulation increased MSC adipogenic potential with greater Oil Red O stained areas. Conclusion: Inducible IL-17A and TNF production by healthy human entheseal CD4+ and CD8+ T-cells was robustly inhibited in vitro by tofacitinib. However, tofacitinib did not impact MSC osteogenesis, but stimulated in vitro MSC adipogenesis, the relevance of which needs further evaluation given that the adipocytes are associated with new bone formation in SpA. tofacitinib JAK-STAT ankylosing spondylitis Medicine R Hannah Rowe verfasserin aut Charlie Bridgewood verfasserin aut Richard J. Cuthbert verfasserin aut Abdulla Watad verfasserin aut Darren Newton verfasserin aut Elena Jones verfasserin aut Dennis McGonagle verfasserin aut In Immuno MDPI AG, 2021 1(2021), 4, Seite 545-557 (DE-627)1768279497 26735601 nnns volume:1 year:2021 number:4 pages:545-557 https://doi.org/10.3390/immuno1040038 kostenfrei https://doaj.org/article/6e2ce4d124004ec2a411bdbe09605234 kostenfrei https://www.mdpi.com/2673-5601/1/4/38 kostenfrei https://doaj.org/toc/2673-5601 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_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 1 2021 4 545-557
allfieldsGer	10.3390/immuno1040038 doi (DE-627)DOAJ019186088 (DE-599)DOAJ6e2ce4d124004ec2a411bdbe09605234 DE-627 ger DE-627 rakwb eng Tobias Russell verfasserin aut Tofacitinib Blocks Entheseal Lymphocyte Activation and Modulates MSC Adipogenesis, but Does Not Directly Affect Chondro- and Osteogenesis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Entheseal spinal inflammation and new bone formation with progressive ankylosis may occur in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). This study evaluated whether JAK inhibition with tofacitinib modulated the key disease associated cytokines, TNF and IL-17A, and whether tofacitinib also modulated bone marrow stromal cell-derived mesenchymal stem cell (MSCs) function, including osteogenesis, since post inflammation new bone formation occurs under these conditions. Methods: Conventional entheseal derived αβ CD4+ and CD8+ T-cells were investigated following anti-CD3/CD28 bead stimulation to determine IL-17A and TNF levels in tofacitinib treated (1000 nM) peri-entheseal bone (PEB) and peripheral blood mononuclear cells (PBMC) using ELISA. Bone marrow stromal cell-derived mesenchymal stem cell (MSC) colony forming units (CFU-F) and multi-lineage potential were evaluated using tofacitinib (dosages ranging between 100, 500, 1000 and 10,000 nM). Results: Induced IL-17A and TNF cytokine production from both entheseal CD4+ T-cells and CD8+ T-cells was effectively inhibited by tofacitinib. Tofacitinib treatment did not impact on CFU-F potential or in vitro chondro- and osteogenesis. However, tofacitinib stimulation increased MSC adipogenic potential with greater Oil Red O stained areas. Conclusion: Inducible IL-17A and TNF production by healthy human entheseal CD4+ and CD8+ T-cells was robustly inhibited in vitro by tofacitinib. However, tofacitinib did not impact MSC osteogenesis, but stimulated in vitro MSC adipogenesis, the relevance of which needs further evaluation given that the adipocytes are associated with new bone formation in SpA. tofacitinib JAK-STAT ankylosing spondylitis Medicine R Hannah Rowe verfasserin aut Charlie Bridgewood verfasserin aut Richard J. Cuthbert verfasserin aut Abdulla Watad verfasserin aut Darren Newton verfasserin aut Elena Jones verfasserin aut Dennis McGonagle verfasserin aut In Immuno MDPI AG, 2021 1(2021), 4, Seite 545-557 (DE-627)1768279497 26735601 nnns volume:1 year:2021 number:4 pages:545-557 https://doi.org/10.3390/immuno1040038 kostenfrei https://doaj.org/article/6e2ce4d124004ec2a411bdbe09605234 kostenfrei https://www.mdpi.com/2673-5601/1/4/38 kostenfrei https://doaj.org/toc/2673-5601 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_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 1 2021 4 545-557
allfieldsSound	10.3390/immuno1040038 doi (DE-627)DOAJ019186088 (DE-599)DOAJ6e2ce4d124004ec2a411bdbe09605234 DE-627 ger DE-627 rakwb eng Tobias Russell verfasserin aut Tofacitinib Blocks Entheseal Lymphocyte Activation and Modulates MSC Adipogenesis, but Does Not Directly Affect Chondro- and Osteogenesis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Entheseal spinal inflammation and new bone formation with progressive ankylosis may occur in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). This study evaluated whether JAK inhibition with tofacitinib modulated the key disease associated cytokines, TNF and IL-17A, and whether tofacitinib also modulated bone marrow stromal cell-derived mesenchymal stem cell (MSCs) function, including osteogenesis, since post inflammation new bone formation occurs under these conditions. Methods: Conventional entheseal derived αβ CD4+ and CD8+ T-cells were investigated following anti-CD3/CD28 bead stimulation to determine IL-17A and TNF levels in tofacitinib treated (1000 nM) peri-entheseal bone (PEB) and peripheral blood mononuclear cells (PBMC) using ELISA. Bone marrow stromal cell-derived mesenchymal stem cell (MSC) colony forming units (CFU-F) and multi-lineage potential were evaluated using tofacitinib (dosages ranging between 100, 500, 1000 and 10,000 nM). Results: Induced IL-17A and TNF cytokine production from both entheseal CD4+ T-cells and CD8+ T-cells was effectively inhibited by tofacitinib. Tofacitinib treatment did not impact on CFU-F potential or in vitro chondro- and osteogenesis. However, tofacitinib stimulation increased MSC adipogenic potential with greater Oil Red O stained areas. Conclusion: Inducible IL-17A and TNF production by healthy human entheseal CD4+ and CD8+ T-cells was robustly inhibited in vitro by tofacitinib. However, tofacitinib did not impact MSC osteogenesis, but stimulated in vitro MSC adipogenesis, the relevance of which needs further evaluation given that the adipocytes are associated with new bone formation in SpA. tofacitinib JAK-STAT ankylosing spondylitis Medicine R Hannah Rowe verfasserin aut Charlie Bridgewood verfasserin aut Richard J. Cuthbert verfasserin aut Abdulla Watad verfasserin aut Darren Newton verfasserin aut Elena Jones verfasserin aut Dennis McGonagle verfasserin aut In Immuno MDPI AG, 2021 1(2021), 4, Seite 545-557 (DE-627)1768279497 26735601 nnns volume:1 year:2021 number:4 pages:545-557 https://doi.org/10.3390/immuno1040038 kostenfrei https://doaj.org/article/6e2ce4d124004ec2a411bdbe09605234 kostenfrei https://www.mdpi.com/2673-5601/1/4/38 kostenfrei https://doaj.org/toc/2673-5601 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_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 1 2021 4 545-557
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author	Tobias Russell
spellingShingle	Tobias Russell misc tofacitinib misc JAK-STAT misc ankylosing spondylitis misc Medicine misc R Tofacitinib Blocks Entheseal Lymphocyte Activation and Modulates MSC Adipogenesis, but Does Not Directly Affect Chondro- and Osteogenesis
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topic_title	Tofacitinib Blocks Entheseal Lymphocyte Activation and Modulates MSC Adipogenesis, but Does Not Directly Affect Chondro- and Osteogenesis tofacitinib JAK-STAT ankylosing spondylitis
topic	misc tofacitinib misc JAK-STAT misc ankylosing spondylitis misc Medicine misc R
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title	Tofacitinib Blocks Entheseal Lymphocyte Activation and Modulates MSC Adipogenesis, but Does Not Directly Affect Chondro- and Osteogenesis
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title_full	Tofacitinib Blocks Entheseal Lymphocyte Activation and Modulates MSC Adipogenesis, but Does Not Directly Affect Chondro- and Osteogenesis
author_sort	Tobias Russell
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author_browse	Tobias Russell Hannah Rowe Charlie Bridgewood Richard J. Cuthbert Abdulla Watad Darren Newton Elena Jones Dennis McGonagle
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title_sort	tofacitinib blocks entheseal lymphocyte activation and modulates msc adipogenesis, but does not directly affect chondro- and osteogenesis
title_auth	Tofacitinib Blocks Entheseal Lymphocyte Activation and Modulates MSC Adipogenesis, but Does Not Directly Affect Chondro- and Osteogenesis
abstract	Entheseal spinal inflammation and new bone formation with progressive ankylosis may occur in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). This study evaluated whether JAK inhibition with tofacitinib modulated the key disease associated cytokines, TNF and IL-17A, and whether tofacitinib also modulated bone marrow stromal cell-derived mesenchymal stem cell (MSCs) function, including osteogenesis, since post inflammation new bone formation occurs under these conditions. Methods: Conventional entheseal derived αβ CD4+ and CD8+ T-cells were investigated following anti-CD3/CD28 bead stimulation to determine IL-17A and TNF levels in tofacitinib treated (1000 nM) peri-entheseal bone (PEB) and peripheral blood mononuclear cells (PBMC) using ELISA. Bone marrow stromal cell-derived mesenchymal stem cell (MSC) colony forming units (CFU-F) and multi-lineage potential were evaluated using tofacitinib (dosages ranging between 100, 500, 1000 and 10,000 nM). Results: Induced IL-17A and TNF cytokine production from both entheseal CD4+ T-cells and CD8+ T-cells was effectively inhibited by tofacitinib. Tofacitinib treatment did not impact on CFU-F potential or in vitro chondro- and osteogenesis. However, tofacitinib stimulation increased MSC adipogenic potential with greater Oil Red O stained areas. Conclusion: Inducible IL-17A and TNF production by healthy human entheseal CD4+ and CD8+ T-cells was robustly inhibited in vitro by tofacitinib. However, tofacitinib did not impact MSC osteogenesis, but stimulated in vitro MSC adipogenesis, the relevance of which needs further evaluation given that the adipocytes are associated with new bone formation in SpA.
abstractGer	Entheseal spinal inflammation and new bone formation with progressive ankylosis may occur in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). This study evaluated whether JAK inhibition with tofacitinib modulated the key disease associated cytokines, TNF and IL-17A, and whether tofacitinib also modulated bone marrow stromal cell-derived mesenchymal stem cell (MSCs) function, including osteogenesis, since post inflammation new bone formation occurs under these conditions. Methods: Conventional entheseal derived αβ CD4+ and CD8+ T-cells were investigated following anti-CD3/CD28 bead stimulation to determine IL-17A and TNF levels in tofacitinib treated (1000 nM) peri-entheseal bone (PEB) and peripheral blood mononuclear cells (PBMC) using ELISA. Bone marrow stromal cell-derived mesenchymal stem cell (MSC) colony forming units (CFU-F) and multi-lineage potential were evaluated using tofacitinib (dosages ranging between 100, 500, 1000 and 10,000 nM). Results: Induced IL-17A and TNF cytokine production from both entheseal CD4+ T-cells and CD8+ T-cells was effectively inhibited by tofacitinib. Tofacitinib treatment did not impact on CFU-F potential or in vitro chondro- and osteogenesis. However, tofacitinib stimulation increased MSC adipogenic potential with greater Oil Red O stained areas. Conclusion: Inducible IL-17A and TNF production by healthy human entheseal CD4+ and CD8+ T-cells was robustly inhibited in vitro by tofacitinib. However, tofacitinib did not impact MSC osteogenesis, but stimulated in vitro MSC adipogenesis, the relevance of which needs further evaluation given that the adipocytes are associated with new bone formation in SpA.
abstract_unstemmed	Entheseal spinal inflammation and new bone formation with progressive ankylosis may occur in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). This study evaluated whether JAK inhibition with tofacitinib modulated the key disease associated cytokines, TNF and IL-17A, and whether tofacitinib also modulated bone marrow stromal cell-derived mesenchymal stem cell (MSCs) function, including osteogenesis, since post inflammation new bone formation occurs under these conditions. Methods: Conventional entheseal derived αβ CD4+ and CD8+ T-cells were investigated following anti-CD3/CD28 bead stimulation to determine IL-17A and TNF levels in tofacitinib treated (1000 nM) peri-entheseal bone (PEB) and peripheral blood mononuclear cells (PBMC) using ELISA. Bone marrow stromal cell-derived mesenchymal stem cell (MSC) colony forming units (CFU-F) and multi-lineage potential were evaluated using tofacitinib (dosages ranging between 100, 500, 1000 and 10,000 nM). Results: Induced IL-17A and TNF cytokine production from both entheseal CD4+ T-cells and CD8+ T-cells was effectively inhibited by tofacitinib. Tofacitinib treatment did not impact on CFU-F potential or in vitro chondro- and osteogenesis. However, tofacitinib stimulation increased MSC adipogenic potential with greater Oil Red O stained areas. Conclusion: Inducible IL-17A and TNF production by healthy human entheseal CD4+ and CD8+ T-cells was robustly inhibited in vitro by tofacitinib. However, tofacitinib did not impact MSC osteogenesis, but stimulated in vitro MSC adipogenesis, the relevance of which needs further evaluation given that the adipocytes are associated with new bone formation in SpA.
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title_short	Tofacitinib Blocks Entheseal Lymphocyte Activation and Modulates MSC Adipogenesis, but Does Not Directly Affect Chondro- and Osteogenesis
url	https://doi.org/10.3390/immuno1040038 https://doaj.org/article/6e2ce4d124004ec2a411bdbe09605234 https://www.mdpi.com/2673-5601/1/4/38 https://doaj.org/toc/2673-5601
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author2	Hannah Rowe Charlie Bridgewood Richard J. Cuthbert Abdulla Watad Darren Newton Elena Jones Dennis McGonagle
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up_date	2024-07-03T22:15:50.462Z
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Tofacitinib treatment did not impact on CFU-F potential or in vitro chondro- and osteogenesis. However, tofacitinib stimulation increased MSC adipogenic potential with greater Oil Red O stained areas. Conclusion: Inducible IL-17A and TNF production by healthy human entheseal CD4+ and CD8+ T-cells was robustly inhibited in vitro by tofacitinib. 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Tofacitinib Blocks Entheseal Lymphocyte Activation and Modulates MSC Adipogenesis, but Does Not Directly Affect Chondro- and Osteogenesis

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