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Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1

T helper type 17 cells (Th17 cells) are major contributors to many autoimmune diseases. In this study, we demonstrate that the germinal center kinase family member MINK1 (misshapen/NIK-related kinase 1) negatively regulates Th17 cell differentiation. The suppressive effect of MINK1 on induction of T...

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Autores principales: Fu, Guotong, Xu, Qin, Qiu, Yuanjun, Jin, Xuexiao, Xu, Ting, Dong, Shunli, Wang, Jianli, Ke, Yuehai, Hu, Hu, Cao, Xuetao, Wang, Di, Cantor, Harvey, Gao, Xiang, Lu, Linrong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413330/
https://www.ncbi.nlm.nih.gov/pubmed/28400474
http://dx.doi.org/10.1084/jem.20161120
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author Fu, Guotong
Xu, Qin
Qiu, Yuanjun
Jin, Xuexiao
Xu, Ting
Dong, Shunli
Wang, Jianli
Ke, Yuehai
Hu, Hu
Cao, Xuetao
Wang, Di
Cantor, Harvey
Gao, Xiang
Lu, Linrong
author_facet Fu, Guotong
Xu, Qin
Qiu, Yuanjun
Jin, Xuexiao
Xu, Ting
Dong, Shunli
Wang, Jianli
Ke, Yuehai
Hu, Hu
Cao, Xuetao
Wang, Di
Cantor, Harvey
Gao, Xiang
Lu, Linrong
author_sort Fu, Guotong
collection PubMed
description T helper type 17 cells (Th17 cells) are major contributors to many autoimmune diseases. In this study, we demonstrate that the germinal center kinase family member MINK1 (misshapen/NIK-related kinase 1) negatively regulates Th17 cell differentiation. The suppressive effect of MINK1 on induction of Th17 cells is mediated by the inhibition of SMAD2 activation through direct phosphorylation of SMAD2 at the T324 residue. The importance of MINK1 to Th17 cell differentiation was strengthened in the animal model of experimental autoimmune encephalomyelitis (EAE). Moreover, we show that the reactive oxygen species (ROS) scavenger N-acetyl cysteine boosts Th17 cell differentiation in a MINK1-dependent manner and exacerbates the severity of EAE. Thus, we have not only established MINK1 as a critical regulator of Th17 cell differentiation, but also clarified that accumulation of ROS may limit the generation of Th17 cells. The contribution of MINK1 to ROS-regulated Th17 cell differentiation may suggest an important mechanism for the development of autoimmune diseases influenced by antioxidant dietary supplements.
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spelling pubmed-54133302017-11-01 Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1 Fu, Guotong Xu, Qin Qiu, Yuanjun Jin, Xuexiao Xu, Ting Dong, Shunli Wang, Jianli Ke, Yuehai Hu, Hu Cao, Xuetao Wang, Di Cantor, Harvey Gao, Xiang Lu, Linrong J Exp Med Research Articles T helper type 17 cells (Th17 cells) are major contributors to many autoimmune diseases. In this study, we demonstrate that the germinal center kinase family member MINK1 (misshapen/NIK-related kinase 1) negatively regulates Th17 cell differentiation. The suppressive effect of MINK1 on induction of Th17 cells is mediated by the inhibition of SMAD2 activation through direct phosphorylation of SMAD2 at the T324 residue. The importance of MINK1 to Th17 cell differentiation was strengthened in the animal model of experimental autoimmune encephalomyelitis (EAE). Moreover, we show that the reactive oxygen species (ROS) scavenger N-acetyl cysteine boosts Th17 cell differentiation in a MINK1-dependent manner and exacerbates the severity of EAE. Thus, we have not only established MINK1 as a critical regulator of Th17 cell differentiation, but also clarified that accumulation of ROS may limit the generation of Th17 cells. The contribution of MINK1 to ROS-regulated Th17 cell differentiation may suggest an important mechanism for the development of autoimmune diseases influenced by antioxidant dietary supplements. The Rockefeller University Press 2017-05-01 /pmc/articles/PMC5413330/ /pubmed/28400474 http://dx.doi.org/10.1084/jem.20161120 Text en © 2017 Fu et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Fu, Guotong
Xu, Qin
Qiu, Yuanjun
Jin, Xuexiao
Xu, Ting
Dong, Shunli
Wang, Jianli
Ke, Yuehai
Hu, Hu
Cao, Xuetao
Wang, Di
Cantor, Harvey
Gao, Xiang
Lu, Linrong
Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1
title Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1
title_full Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1
title_fullStr Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1
title_full_unstemmed Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1
title_short Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1
title_sort suppression of th17 cell differentiation by misshapen/nik-related kinase mink1
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413330/
https://www.ncbi.nlm.nih.gov/pubmed/28400474
http://dx.doi.org/10.1084/jem.20161120
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