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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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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. |
format | Online Article Text |
id | pubmed-5413330 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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