Cutting Edge: IFN-γR Signaling in Non–T Cell Targets Regulates T Cell–Mediated Intestinal Inflammation through Multiple Mechanisms

Naive CD4 T cells transferred into lymphopenic mice undergo spontaneous proliferation and induce chronic inflammation in the intestine. Cellular mechanisms regulating the proliferative and inflammatory processes are not fully understood. In this study, we report that IFN-γ signaling in host cells plays a major role in limiting both T cell expansion and T cell-induced intestinal inflammation. However, the role of IFN-γ appears to differ depending on the target cells. IFN-γ signaling in dendritic cells controls T cell expansion, whereas IFN-γ signaling in neutrophils seems to regulate both T cell expansion and inflammation. IFN-γ signaling in nonhematopoietic cells may control inflammation. Therefore, our results suggest novel immunoregulatory functions for IFN-γ to orchestrate colitogenic T cell responses through its distinct action on different non-T cell target cells.