A protective role of IFN-γ in T cell-mediated colitis by regulation of Treg/Th17 via induction of indoleamine-2,3-deoxygenase

Abstract

Abstract IFN-γ is an important Th1 type cytokine and has a paradoxical effect on the pathogenesis of several chronic inflammatory disorders, including inflammatory bowel disease. Here we demonstrate that IFN-γ plays a protective effect on the model of T cell-mediated colitis. Compare with wild-type control, adoptive transfer of CD4+CD62L+ naïve T cells isolated from IFN-γ−/−mice into Rag1−/−mice induced a more severe wasting disease, correlating with increased expression of Th17 cells but decreased expression of Foxp3+ T regulatory cells in colon tissue and peripheral lymphoid organs. Additionally, infusion of CD4+CD62L+ naïve T cells isolated from IFN-γ receptor knock-out mice into recipient Rag1−/−mice also elicited a more severe wasting disease when compared to infusion of naïve T cells isolated from wild-type mice. IFN-γ induced indoleamine-2,3-dioxgenase (IDO), an enzyme in the metabolism of tryptophan, plays a critical roles in immune responses regulating the balance between Treg and Th17 cells. Our data suggest that IFN-γ provides a protective function in T cell-mediated intestinal inflammation by regulation of Treg and Th17 via the induction of IDO.