T cell-mediated immunity in the intestine is stringently controlled to ensure proper immunity against pathogenic microbes and to prevent autoimmunity,a known cause of inflammatory bowel disease.However,precisely how T cells regulate intestine immunity remains to be fully understood.In this study,we found that mitogen-activated protein kinase kinase kinase 2 (MAP3K2) is required for the CD4+ T cell-mediated inflammation in the intestine.Using a T cell transfer colitis model,we found that MAP3K2-deficient na(i)ve CD4+ T cells had a dramatically reduced ability to induce colitis compared to wild type T cells.In addition,significantly fewer IFN-γ-but more IL-17A-producing CD4+ T cells in the intestines of mice receiving MAP3K2-deficient T cells than in those from mice receiving wild type T cells was observed.Interestingly,under well-defined in vitro differentiation conditions,MAP3K2-defieient na(i)ve T cells were not impaired in their ability to differentiate into Th1,Th17 and Treg.Furthermore,the MAP3K2-regulated colitis severity was mediated by Th1 but not Th17 cells in the intestine.At the molecular level,we showed that MAP3K2-mediated Thl cell differentiation in the intestine was regulated by IL-18 and required specific JNK activation.Together,our study reveals a novel regulatory role of MAP3K2 in intestinal T cell immunity via the IL-l 8-MAP3K2-JNK axis and may provide a novel target for intervention in T cell-mediated colitis.