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.