Tristetraprolin Regulates T H 17 Cell Function and Ameliorates DSS-Induced Colitis in Mice.

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.
(Copyright © 2020 Peng, Ning, Wang, Lai, Wei, Stumpo, Blackshear, Fu, Hou, Hoft and Liu.)