Inhibition of Acute Graft-versus-Host Disease with Retention of Graft-versus-Tumor Effects by Dimethyl Fumarate

Acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF), an activator of Nrf2, has been shown to have anti-inflammatory and immunomodulatory pr...
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Autor*in:	Jingjing Han [verfasserIn] Shoubao Ma [verfasserIn] Huanle Gong [verfasserIn] Shuangzhu Liu [verfasserIn] Lei Lei [verfasserIn] Bo Hu [verfasserIn] Yang Xu [verfasserIn] Haiyan Liu [verfasserIn] Depei Wu [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Schlagwörter:	acute graft-versus-host disease graft-versus-leukemia Nrf2 dimethyl fumarate Treg cells

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 8(2017)
Übergeordnetes Werk:	volume:8 ; year:2017

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2017.01605

Katalog-ID:	DOAJ058096914

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520			\|a Acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF), an activator of Nrf2, has been shown to have anti-inflammatory and immunomodulatory properties without significant immunosuppression. We therefore hypothesized that DMF could be potentially harnessed for the treatment of aGVHD with retention of graft-versus-tumor effect. In this study, we showed that DMF significantly inhibited alloreactive T cell responses in vitro in mixed lymphocyte reaction assay. Administration of DMF significantly alleviated the severity, histological damage, and the overall mortality of aGVHD in an MHC-mismatched aGVHD model. DMF administration reduced the activation and effector function of donor T cells in vitro and in vivo. In addition, DMF treatment upregulated antioxidant enzymes heme oxygenase-1 and glutathione S-transferase-α1 expressions. Furthermore, DMF treatment markedly increased the frequencies of Treg cells. Depletion of CD25+ cells in DMF recipients aggravated aGVHD mortality compared with IgG control recipients. DMF could promote Treg cell differentiation in a dose dependent manner by upregulating TGF-β expression in vitro. Most importantly, DMF administration preserved graft-versus-leukemia effect after bone marrow transplantation. In conclusion, our findings demonstrated DMF as a promising agent for the prevention of aGVHD after allo-HSCT.
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Indexfelder

author_variant	j h jh j h jh j h jh s m sm s m sm h g hg s l sl s l sl l l ll l l ll l l ll b h bh b h bh y x yx y x yx y x yx h l hl d w dw d w dw d w dw
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allfields	10.3389/fimmu.2017.01605 doi (DE-627)DOAJ058096914 (DE-599)DOAJ3bb5cf6e6201494cb91f4b4dd5086652 DE-627 ger DE-627 rakwb eng RC581-607 Jingjing Han verfasserin aut Inhibition of Acute Graft-versus-Host Disease with Retention of Graft-versus-Tumor Effects by Dimethyl Fumarate 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF), an activator of Nrf2, has been shown to have anti-inflammatory and immunomodulatory properties without significant immunosuppression. We therefore hypothesized that DMF could be potentially harnessed for the treatment of aGVHD with retention of graft-versus-tumor effect. In this study, we showed that DMF significantly inhibited alloreactive T cell responses in vitro in mixed lymphocyte reaction assay. Administration of DMF significantly alleviated the severity, histological damage, and the overall mortality of aGVHD in an MHC-mismatched aGVHD model. DMF administration reduced the activation and effector function of donor T cells in vitro and in vivo. In addition, DMF treatment upregulated antioxidant enzymes heme oxygenase-1 and glutathione S-transferase-α1 expressions. Furthermore, DMF treatment markedly increased the frequencies of Treg cells. Depletion of CD25+ cells in DMF recipients aggravated aGVHD mortality compared with IgG control recipients. DMF could promote Treg cell differentiation in a dose dependent manner by upregulating TGF-β expression in vitro. Most importantly, DMF administration preserved graft-versus-leukemia effect after bone marrow transplantation. In conclusion, our findings demonstrated DMF as a promising agent for the prevention of aGVHD after allo-HSCT. acute graft-versus-host disease graft-versus-leukemia Nrf2 dimethyl fumarate Treg cells Immunologic diseases. Allergy Jingjing Han verfasserin aut Jingjing Han verfasserin aut Shoubao Ma verfasserin aut Shoubao Ma verfasserin aut Huanle Gong verfasserin aut Shuangzhu Liu verfasserin aut Shuangzhu Liu verfasserin aut Lei Lei verfasserin aut Lei Lei verfasserin aut Lei Lei verfasserin aut Bo Hu verfasserin aut Bo Hu verfasserin aut Yang Xu verfasserin aut Yang Xu verfasserin aut Yang Xu verfasserin aut Haiyan Liu verfasserin aut Depei Wu verfasserin aut Depei Wu verfasserin aut Depei Wu verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.01605 kostenfrei https://doaj.org/article/3bb5cf6e6201494cb91f4b4dd5086652 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.01605/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 8 2017
spelling	10.3389/fimmu.2017.01605 doi (DE-627)DOAJ058096914 (DE-599)DOAJ3bb5cf6e6201494cb91f4b4dd5086652 DE-627 ger DE-627 rakwb eng RC581-607 Jingjing Han verfasserin aut Inhibition of Acute Graft-versus-Host Disease with Retention of Graft-versus-Tumor Effects by Dimethyl Fumarate 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF), an activator of Nrf2, has been shown to have anti-inflammatory and immunomodulatory properties without significant immunosuppression. We therefore hypothesized that DMF could be potentially harnessed for the treatment of aGVHD with retention of graft-versus-tumor effect. In this study, we showed that DMF significantly inhibited alloreactive T cell responses in vitro in mixed lymphocyte reaction assay. Administration of DMF significantly alleviated the severity, histological damage, and the overall mortality of aGVHD in an MHC-mismatched aGVHD model. DMF administration reduced the activation and effector function of donor T cells in vitro and in vivo. In addition, DMF treatment upregulated antioxidant enzymes heme oxygenase-1 and glutathione S-transferase-α1 expressions. Furthermore, DMF treatment markedly increased the frequencies of Treg cells. Depletion of CD25+ cells in DMF recipients aggravated aGVHD mortality compared with IgG control recipients. DMF could promote Treg cell differentiation in a dose dependent manner by upregulating TGF-β expression in vitro. Most importantly, DMF administration preserved graft-versus-leukemia effect after bone marrow transplantation. In conclusion, our findings demonstrated DMF as a promising agent for the prevention of aGVHD after allo-HSCT. acute graft-versus-host disease graft-versus-leukemia Nrf2 dimethyl fumarate Treg cells Immunologic diseases. Allergy Jingjing Han verfasserin aut Jingjing Han verfasserin aut Shoubao Ma verfasserin aut Shoubao Ma verfasserin aut Huanle Gong verfasserin aut Shuangzhu Liu verfasserin aut Shuangzhu Liu verfasserin aut Lei Lei verfasserin aut Lei Lei verfasserin aut Lei Lei verfasserin aut Bo Hu verfasserin aut Bo Hu verfasserin aut Yang Xu verfasserin aut Yang Xu verfasserin aut Yang Xu verfasserin aut Haiyan Liu verfasserin aut Depei Wu verfasserin aut Depei Wu verfasserin aut Depei Wu verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.01605 kostenfrei https://doaj.org/article/3bb5cf6e6201494cb91f4b4dd5086652 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.01605/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 8 2017
allfields_unstemmed	10.3389/fimmu.2017.01605 doi (DE-627)DOAJ058096914 (DE-599)DOAJ3bb5cf6e6201494cb91f4b4dd5086652 DE-627 ger DE-627 rakwb eng RC581-607 Jingjing Han verfasserin aut Inhibition of Acute Graft-versus-Host Disease with Retention of Graft-versus-Tumor Effects by Dimethyl Fumarate 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF), an activator of Nrf2, has been shown to have anti-inflammatory and immunomodulatory properties without significant immunosuppression. We therefore hypothesized that DMF could be potentially harnessed for the treatment of aGVHD with retention of graft-versus-tumor effect. In this study, we showed that DMF significantly inhibited alloreactive T cell responses in vitro in mixed lymphocyte reaction assay. Administration of DMF significantly alleviated the severity, histological damage, and the overall mortality of aGVHD in an MHC-mismatched aGVHD model. DMF administration reduced the activation and effector function of donor T cells in vitro and in vivo. In addition, DMF treatment upregulated antioxidant enzymes heme oxygenase-1 and glutathione S-transferase-α1 expressions. Furthermore, DMF treatment markedly increased the frequencies of Treg cells. Depletion of CD25+ cells in DMF recipients aggravated aGVHD mortality compared with IgG control recipients. DMF could promote Treg cell differentiation in a dose dependent manner by upregulating TGF-β expression in vitro. Most importantly, DMF administration preserved graft-versus-leukemia effect after bone marrow transplantation. In conclusion, our findings demonstrated DMF as a promising agent for the prevention of aGVHD after allo-HSCT. acute graft-versus-host disease graft-versus-leukemia Nrf2 dimethyl fumarate Treg cells Immunologic diseases. Allergy Jingjing Han verfasserin aut Jingjing Han verfasserin aut Shoubao Ma verfasserin aut Shoubao Ma verfasserin aut Huanle Gong verfasserin aut Shuangzhu Liu verfasserin aut Shuangzhu Liu verfasserin aut Lei Lei verfasserin aut Lei Lei verfasserin aut Lei Lei verfasserin aut Bo Hu verfasserin aut Bo Hu verfasserin aut Yang Xu verfasserin aut Yang Xu verfasserin aut Yang Xu verfasserin aut Haiyan Liu verfasserin aut Depei Wu verfasserin aut Depei Wu verfasserin aut Depei Wu verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.01605 kostenfrei https://doaj.org/article/3bb5cf6e6201494cb91f4b4dd5086652 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.01605/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 8 2017
allfieldsGer	10.3389/fimmu.2017.01605 doi (DE-627)DOAJ058096914 (DE-599)DOAJ3bb5cf6e6201494cb91f4b4dd5086652 DE-627 ger DE-627 rakwb eng RC581-607 Jingjing Han verfasserin aut Inhibition of Acute Graft-versus-Host Disease with Retention of Graft-versus-Tumor Effects by Dimethyl Fumarate 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF), an activator of Nrf2, has been shown to have anti-inflammatory and immunomodulatory properties without significant immunosuppression. We therefore hypothesized that DMF could be potentially harnessed for the treatment of aGVHD with retention of graft-versus-tumor effect. In this study, we showed that DMF significantly inhibited alloreactive T cell responses in vitro in mixed lymphocyte reaction assay. Administration of DMF significantly alleviated the severity, histological damage, and the overall mortality of aGVHD in an MHC-mismatched aGVHD model. DMF administration reduced the activation and effector function of donor T cells in vitro and in vivo. In addition, DMF treatment upregulated antioxidant enzymes heme oxygenase-1 and glutathione S-transferase-α1 expressions. Furthermore, DMF treatment markedly increased the frequencies of Treg cells. Depletion of CD25+ cells in DMF recipients aggravated aGVHD mortality compared with IgG control recipients. DMF could promote Treg cell differentiation in a dose dependent manner by upregulating TGF-β expression in vitro. Most importantly, DMF administration preserved graft-versus-leukemia effect after bone marrow transplantation. In conclusion, our findings demonstrated DMF as a promising agent for the prevention of aGVHD after allo-HSCT. acute graft-versus-host disease graft-versus-leukemia Nrf2 dimethyl fumarate Treg cells Immunologic diseases. Allergy Jingjing Han verfasserin aut Jingjing Han verfasserin aut Shoubao Ma verfasserin aut Shoubao Ma verfasserin aut Huanle Gong verfasserin aut Shuangzhu Liu verfasserin aut Shuangzhu Liu verfasserin aut Lei Lei verfasserin aut Lei Lei verfasserin aut Lei Lei verfasserin aut Bo Hu verfasserin aut Bo Hu verfasserin aut Yang Xu verfasserin aut Yang Xu verfasserin aut Yang Xu verfasserin aut Haiyan Liu verfasserin aut Depei Wu verfasserin aut Depei Wu verfasserin aut Depei Wu verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.01605 kostenfrei https://doaj.org/article/3bb5cf6e6201494cb91f4b4dd5086652 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.01605/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 8 2017
allfieldsSound	10.3389/fimmu.2017.01605 doi (DE-627)DOAJ058096914 (DE-599)DOAJ3bb5cf6e6201494cb91f4b4dd5086652 DE-627 ger DE-627 rakwb eng RC581-607 Jingjing Han verfasserin aut Inhibition of Acute Graft-versus-Host Disease with Retention of Graft-versus-Tumor Effects by Dimethyl Fumarate 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF), an activator of Nrf2, has been shown to have anti-inflammatory and immunomodulatory properties without significant immunosuppression. We therefore hypothesized that DMF could be potentially harnessed for the treatment of aGVHD with retention of graft-versus-tumor effect. In this study, we showed that DMF significantly inhibited alloreactive T cell responses in vitro in mixed lymphocyte reaction assay. Administration of DMF significantly alleviated the severity, histological damage, and the overall mortality of aGVHD in an MHC-mismatched aGVHD model. DMF administration reduced the activation and effector function of donor T cells in vitro and in vivo. In addition, DMF treatment upregulated antioxidant enzymes heme oxygenase-1 and glutathione S-transferase-α1 expressions. Furthermore, DMF treatment markedly increased the frequencies of Treg cells. Depletion of CD25+ cells in DMF recipients aggravated aGVHD mortality compared with IgG control recipients. DMF could promote Treg cell differentiation in a dose dependent manner by upregulating TGF-β expression in vitro. Most importantly, DMF administration preserved graft-versus-leukemia effect after bone marrow transplantation. In conclusion, our findings demonstrated DMF as a promising agent for the prevention of aGVHD after allo-HSCT. acute graft-versus-host disease graft-versus-leukemia Nrf2 dimethyl fumarate Treg cells Immunologic diseases. Allergy Jingjing Han verfasserin aut Jingjing Han verfasserin aut Shoubao Ma verfasserin aut Shoubao Ma verfasserin aut Huanle Gong verfasserin aut Shuangzhu Liu verfasserin aut Shuangzhu Liu verfasserin aut Lei Lei verfasserin aut Lei Lei verfasserin aut Lei Lei verfasserin aut Bo Hu verfasserin aut Bo Hu verfasserin aut Yang Xu verfasserin aut Yang Xu verfasserin aut Yang Xu verfasserin aut Haiyan Liu verfasserin aut Depei Wu verfasserin aut Depei Wu verfasserin aut Depei Wu verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.01605 kostenfrei https://doaj.org/article/3bb5cf6e6201494cb91f4b4dd5086652 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.01605/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 8 2017
language	English
source	In Frontiers in Immunology 8(2017) volume:8 year:2017
sourceStr	In Frontiers in Immunology 8(2017) volume:8 year:2017
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	acute graft-versus-host disease graft-versus-leukemia Nrf2 dimethyl fumarate Treg cells Immunologic diseases. Allergy
isfreeaccess_bool	true
container_title	Frontiers in Immunology
authorswithroles_txt_mv	Jingjing Han @@aut@@ Shoubao Ma @@aut@@ Huanle Gong @@aut@@ Shuangzhu Liu @@aut@@ Lei Lei @@aut@@ Bo Hu @@aut@@ Yang Xu @@aut@@ Haiyan Liu @@aut@@ Depei Wu @@aut@@
publishDateDaySort_date	2017-01-01T00:00:00Z
hierarchy_top_id	657998354
id	DOAJ058096914
language_de	englisch
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callnumber-first	R - Medicine
author	Jingjing Han
spellingShingle	Jingjing Han misc RC581-607 misc acute graft-versus-host disease misc graft-versus-leukemia misc Nrf2 misc dimethyl fumarate misc Treg cells misc Immunologic diseases. Allergy Inhibition of Acute Graft-versus-Host Disease with Retention of Graft-versus-Tumor Effects by Dimethyl Fumarate
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topic_title	RC581-607 Inhibition of Acute Graft-versus-Host Disease with Retention of Graft-versus-Tumor Effects by Dimethyl Fumarate acute graft-versus-host disease graft-versus-leukemia Nrf2 dimethyl fumarate Treg cells
topic	misc RC581-607 misc acute graft-versus-host disease misc graft-versus-leukemia misc Nrf2 misc dimethyl fumarate misc Treg cells misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc acute graft-versus-host disease misc graft-versus-leukemia misc Nrf2 misc dimethyl fumarate misc Treg cells misc Immunologic diseases. Allergy
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title	Inhibition of Acute Graft-versus-Host Disease with Retention of Graft-versus-Tumor Effects by Dimethyl Fumarate
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title_full	Inhibition of Acute Graft-versus-Host Disease with Retention of Graft-versus-Tumor Effects by Dimethyl Fumarate
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author_browse	Jingjing Han Shoubao Ma Huanle Gong Shuangzhu Liu Lei Lei Bo Hu Yang Xu Haiyan Liu Depei Wu
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title_sort	inhibition of acute graft-versus-host disease with retention of graft-versus-tumor effects by dimethyl fumarate
callnumber	RC581-607
title_auth	Inhibition of Acute Graft-versus-Host Disease with Retention of Graft-versus-Tumor Effects by Dimethyl Fumarate
abstract	Acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF), an activator of Nrf2, has been shown to have anti-inflammatory and immunomodulatory properties without significant immunosuppression. We therefore hypothesized that DMF could be potentially harnessed for the treatment of aGVHD with retention of graft-versus-tumor effect. In this study, we showed that DMF significantly inhibited alloreactive T cell responses in vitro in mixed lymphocyte reaction assay. Administration of DMF significantly alleviated the severity, histological damage, and the overall mortality of aGVHD in an MHC-mismatched aGVHD model. DMF administration reduced the activation and effector function of donor T cells in vitro and in vivo. In addition, DMF treatment upregulated antioxidant enzymes heme oxygenase-1 and glutathione S-transferase-α1 expressions. Furthermore, DMF treatment markedly increased the frequencies of Treg cells. Depletion of CD25+ cells in DMF recipients aggravated aGVHD mortality compared with IgG control recipients. DMF could promote Treg cell differentiation in a dose dependent manner by upregulating TGF-β expression in vitro. Most importantly, DMF administration preserved graft-versus-leukemia effect after bone marrow transplantation. In conclusion, our findings demonstrated DMF as a promising agent for the prevention of aGVHD after allo-HSCT.
abstractGer	Acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF), an activator of Nrf2, has been shown to have anti-inflammatory and immunomodulatory properties without significant immunosuppression. We therefore hypothesized that DMF could be potentially harnessed for the treatment of aGVHD with retention of graft-versus-tumor effect. In this study, we showed that DMF significantly inhibited alloreactive T cell responses in vitro in mixed lymphocyte reaction assay. Administration of DMF significantly alleviated the severity, histological damage, and the overall mortality of aGVHD in an MHC-mismatched aGVHD model. DMF administration reduced the activation and effector function of donor T cells in vitro and in vivo. In addition, DMF treatment upregulated antioxidant enzymes heme oxygenase-1 and glutathione S-transferase-α1 expressions. Furthermore, DMF treatment markedly increased the frequencies of Treg cells. Depletion of CD25+ cells in DMF recipients aggravated aGVHD mortality compared with IgG control recipients. DMF could promote Treg cell differentiation in a dose dependent manner by upregulating TGF-β expression in vitro. Most importantly, DMF administration preserved graft-versus-leukemia effect after bone marrow transplantation. In conclusion, our findings demonstrated DMF as a promising agent for the prevention of aGVHD after allo-HSCT.
abstract_unstemmed	Acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF), an activator of Nrf2, has been shown to have anti-inflammatory and immunomodulatory properties without significant immunosuppression. We therefore hypothesized that DMF could be potentially harnessed for the treatment of aGVHD with retention of graft-versus-tumor effect. In this study, we showed that DMF significantly inhibited alloreactive T cell responses in vitro in mixed lymphocyte reaction assay. Administration of DMF significantly alleviated the severity, histological damage, and the overall mortality of aGVHD in an MHC-mismatched aGVHD model. DMF administration reduced the activation and effector function of donor T cells in vitro and in vivo. In addition, DMF treatment upregulated antioxidant enzymes heme oxygenase-1 and glutathione S-transferase-α1 expressions. Furthermore, DMF treatment markedly increased the frequencies of Treg cells. Depletion of CD25+ cells in DMF recipients aggravated aGVHD mortality compared with IgG control recipients. DMF could promote Treg cell differentiation in a dose dependent manner by upregulating TGF-β expression in vitro. Most importantly, DMF administration preserved graft-versus-leukemia effect after bone marrow transplantation. In conclusion, our findings demonstrated DMF as a promising agent for the prevention of aGVHD after allo-HSCT.
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title_short	Inhibition of Acute Graft-versus-Host Disease with Retention of Graft-versus-Tumor Effects by Dimethyl Fumarate
url	https://doi.org/10.3389/fimmu.2017.01605 https://doaj.org/article/3bb5cf6e6201494cb91f4b4dd5086652 http://journal.frontiersin.org/article/10.3389/fimmu.2017.01605/full https://doaj.org/toc/1664-3224
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author2	Jingjing Han Shoubao Ma Huanle Gong Shuangzhu Liu Lei Lei Bo Hu Yang Xu Haiyan Liu Depei Wu
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up_date	2024-07-03T15:58:32.654Z
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Inhibition of Acute Graft-versus-Host Disease with Retention of Graft-versus-Tumor Effects by Dimethyl Fumarate

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