T-bet expression by Th cells promotes type 1 inflammation but is dispensable for the clinical manifestation of murine colitis

The transcription factor “T-box expressed in T cells” (T-bet) is highly expressed by Th cells isolated from the inflamed intestine of Crohn’s disease patients. Previous analyses have suggested that T-bet is required for the induction of murine T cell-induced colitis. Here we demonstrate that this is not the case. T-bet-deficient Th cells efficiently induce colitis, with the clinical manifestation of weight loss, diarrhea and histopathological changes of the colonic mucosa. T-bet is regulating, however, the survival and positioning of the Th cells, their chemokine and chemokine receptor expression, their attraction of monocytes and macrophages into the inflamed colon, and the differentiation of monocytes and macrophages to the M1 type. T-bet-deficient Th cells show increased expression of IL-17, yet, remarkably, retain expression of IFN-γ. Th cell-derived IFN-γ, however, is not required to induce colitis, as we show using IFN-γ-deficient Th cells. Overall, we demonstrate that T-bet is not essential for the induction of murine colitis, but it is critical for the induction of type 1 inflammation.