Cutting Edge: Ubiquitin-Specific Protease 4 Promotes Th17 Cell Function under Inflammation by Deubiquitinating and Stabilizing RORγt

被引：65

作者：

Yang, Jing ^{[1
]}

Xu, Peng ^{[2
]}

Han, Lei ^{[3
]}

Guo, Zhixiang ^{[2
]}

Wang, Xiuwen ^{[3
]}

Chen, Zuojia ^{[1
]}

Nie, Jia ^{[1
]}

Yin, Shuying ^{[1
]}

Piccioni, Miranda ^{[1
]}

Tsun, Andy ^{[1
]}

Lv, Ling ^{[3
]}

Ge, Shenglin ^{[2
]}

Li, Bin ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol,Unit Mol Immunol, Shanghai 200025, Peoples R China

[2] Anhui Med Univ, Affiliated Hosp 1, Dept Cardiovasc Surg, Hefei 230032, Peoples R China

[3] Fudan Univ, Div Rheumatol, Huashan Hosp, Shanghai 200040, Peoples R China

来源：

JOURNAL OF IMMUNOLOGY | 2015年 / 194卷 / 09期

关键词：

TRANSCRIPTION FACTOR FOXP3; REGULATORY T; TGF-BETA; DIFFERENTIATION; RECEPTOR; T(H)17; BALANCE; IL-6;

D O I：

10.4049/jimmunol.1401451

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

ROR gamma t is a key transcription factor that controls the development and function of inflammatory Th17. The mechanisms that regulate RORgt stability remain unclear. We report that Th17 cells highly express the deubiquitinase ubiquitin-specific protease (USP) 4, which is essential for maintaining RORgt and Th17 cell function. Inhibition of the catalytic activity of USP4 with vialinin A, a compound derived from Chinese traditional medicine, dampened Th17 differentiation. USP4 interacted and deubiquitinated K48-linked polyubiquitination of RORgt, thereby promoting ROR gamma t function and IL-17A transcription. Interestingly, TGF-beta plus IL-6 enhanced USP4-mediated deubiquitination of ROR gamma t. Moreover, USP4 and IL-17 mRNA, but not RORgt mRNA, were significantly elevated in CD4(+) T cells from patients with rheumatic heart disease. Thus, USP4 could be a novel therapeutic target for the treatment of Th17-modulated autoimmune diseases.

引用

页码：4094 / 4097

页数：4