Tristetraprolin Regulates TH17 Cell Function and Ameliorates DSS-Induced Colitis in Mice

被引：9
作者：
Peng, Hui [1 ]
Ning, Huan [1 ]
Wang, Qinghong [1 ]
Lai, Jinping [2 ]
Wei, Lin [3 ]
Stumpo, Deborah J. [4 ]
Blackshear, Perry J. [4 ]
Fu, Mingui [5 ,6 ]
Hou, Rong [1 ]
Hoft, Daniel F. [1 ]
Liu, Jianguo [1 ]
机构：
[1] St Louis Univ, Sch Med, Dept Internal Med, Div Infect Dis Allergy & Immunol, St Louis, MO 63103 USA
[2] St Louis Univ, Sch Med, Dept Pathol, St Louis, MO 63104 USA
[3] Hebei Med Univ, Sch Basic Med, Dept Immunol, Shijiazhuang, Hebei, Peoples R China
[4] NIEHS, Res Triangle Pk, NC USA
[5] Univ Missouri, Sch Med, Shock Trauma Res Ctr, Kansas City, MO 64108 USA
[6] Univ Missouri, Sch Med, Dept Basic Med Sci, Kansas City, MO 64108 USA
来源：
FRONTIERS IN IMMUNOLOGY | 2020年 / 11卷
基金：
美国国家卫生研究院;
关键词：
tristetraprolin; RNA-binding protein; IL-17; mRNA decay; T(H)17; DSS; colitis; AU-RICH ELEMENTS; MESSENGER-RNA STABILITY; ZINC-FINGER PROTEINS; T-CELLS; 3'-UNTRANSLATED REGION; IL-23; EXPRESSION; GENE-EXPRESSION; TNF-ALPHA; GM-CSF; IL-17;
D O I：
10.3389/fimmu.2020.01952
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(H)17 cells have been extensively investigated in inflammation, autoimmune diseases, and cancer. The precise molecular mechanisms for T(H)17 cell regulation, however, remain elusive, especially regulation at the post-transcriptional level. Tristetraprolin (TTP) is an RNA-binding protein important for degradation of the mRNAs encoding several proinflammatory cytokines. With newly generated T cell-specific TTP conditional knockout mice (CD4(Cre)TTP(f/f)), we found that aging CD4(Cre)TTP(f/f)mice displayed an increase of IL-17A in serum and spontaneously developed chronic skin inflammation along with increased effector T(H)17 cells in the affected skin. TTP inhibited T(H)17 cell development and function by promoting IL-17A mRNA degradation. In a DSS-induced colitis model, CD4(Cre)TTP(f/f)mice displayed severe colitis and had more T(H)17 cells and serum IL-17A compared with wild-type mice. Furthermore, neutralization of IL-17A reduced the severity of colitis. Our results reveal a new mechanism for regulating T(H)17 function and T(H)17-mediated inflammation post-transcriptionally by TTP, suggests that TTP might be a novel therapeutic target for the treatment of T(H)17-mediated diseases.
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页数：12
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