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

被引：51

作者：

Fu, Guotong ^{[1
,2
]}

Xu, Qin ^{[1
,2
]}

Qiu, Yuanjun ^{[1
,2
]}

Jin, Xuexiao ^{[1
,2
]}

Xu, Ting ^{[1
,2
]}

Dong, Shunli ^{[7
]}

Wang, Jianli ^{[1
]}

Ke, Yuehai ^{[2
,3
]}

Hu, Hu ^{[3
]}

Cao, Xuetao ^{[1
,8
,9
]}

Wang, Di ^{[1
,2
]}

Cantor, Harvey ^{[10
,11
]}

Gao, Xiang ^{[12
]}

Lu, Linrong ^{[1
,2
,4
,5
,6
]}

机构：

[1] Zhejiang Univ, Univ Edinburgh Inst, Inst Immunol, Edinburgh, Midlothian, Scotland

[2] Zhejiang Univ, Univ Edinburgh Inst, Program Mol & Cellular Biol, Edinburgh, Midlothian, Scotland

[3] Zhejiang Univ, Univ Edinburgh Inst, Dept Pathol & Pathophysiol, Edinburgh, Midlothian, Scotland

[4] Zhejiang Univ, Univ Edinburgh Inst, Innovat Ctr Cell Signaling Network, Edinburgh, Midlothian, Scotland

[5] Zhejiang Univ, Univ Edinburgh Inst, Edinburgh, Midlothian, Scotland

[6] Zhejiang Univ, Sch Med, Dr Li Dak Sum & Yip Yio Chin Ctr Stem Cell & Reg, Hangzhou 310058, Zhejiang, Peoples R China

[7] Zhejiang Univ, Inst Life Sci, Hangzhou 310058, Zhejiang, Peoples R China

[8] Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China

[9] Second Mil Med Univ, Natl Key Lab Med Immunol, Shanghai 200433, Peoples R China

[10] Harvard Med Sch, Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA

[11] Harvard Med Sch, Dept Microbiol & Immunol, Div Immunol, Boston, MA 02115 USA

[12] Nanjing Univ, Model Anim Res Ctr, Key Lab Model Anim Dis Study, Minist Educ, Nanjing 210061, Jiangsu, Peoples R China

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2017年 / 214卷 / 05期

基金：

中国国家自然科学基金;

关键词：

REGULATORY T-CELLS; PATHOGENIC T(H)17 CELLS; TGF-BETA; AUTOIMMUNE-DISEASE; EPITHELIAL-CELLS; INFLAMMATION; ENCEPHALOMYELITIS; GENERATION; INDUCTION; LINEAGE;

D O I：

10.1084/jem.20161120

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：1453 / 1469

页数：17

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