AUTHOR=Peng Hui , Ning Huan , Wang Qinghong , Lai Jinping , Wei Lin , Stumpo Deborah J. , Blackshear Perry J. , Fu Mingui , Hou Rong , Hoft Daniel F. , Liu Jianguo 

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

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01952

DOI=10.3389/fimmu.2020.01952

ISSN=1664-3224

ABSTRACT=<p>T<sub>H</sub>17 cells have been extensively investigated in inflammation, autoimmune diseases, and cancer. The precise molecular mechanisms for T<sub>H</sub>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<sup>Cre</sup>TTP<sup>f/f</sup>), we found that aging CD4<sup>Cre</sup>TTP<sup>f/f</sup> mice displayed an increase of IL-17A in serum and spontaneously developed chronic skin inflammation along with increased effector T<sub>H</sub>17 cells in the affected skin. TTP inhibited T<sub>H</sub>17 cell development and function by promoting IL-17A mRNA degradation. In a DSS-induced colitis model, CD4<sup>Cre</sup>TTP<sup>f/f</sup> mice displayed severe colitis and had more T<sub>H</sub>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<sub>H</sub>17 function and T<sub>H</sub>17-mediated inflammation post-transcriptionally by TTP, suggests that TTP might be a novel therapeutic target for the treatment of T<sub>H</sub>17-mediated diseases.</p>