Tristetraprolin Regulates T17 Cell Function and Ameliorates DSS-Induced Colitis in Mice.

T17 cells have been extensively investigated in inflammation, autoimmune diseases, and cancer. The precise molecular mechanisms for T17 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 (CD4TTP), we found that aging CD4TTP mice displayed an increase of IL-17A in serum and spontaneously developed chronic skin inflammation along with increased effector T17 cells in the affected skin. TTP inhibited T17 cell development and function by promoting IL-17A mRNA degradation. In a DSS-induced colitis model, CD4TTP mice displayed severe colitis and had more T17 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 T17 function and T17-mediated inflammation post-transcriptionally by TTP, suggests that TTP might be a novel therapeutic target for the treatment of T17-mediated diseases.