Interleukin-23 Drives Intestinal Inflammation through Direct Activity on T Cells.
Immunity. 2010 Aug 27;33(2):279-288
Authors: Ahern PP, Schiering C, Buonocore S, McGeachy MJ, Cua DJ, Maloy KJ, Powrie F
Mutations in the IL23R gene are linked to inflammatory bowel disease susceptibility. Experimental models have shown that interleukin-23 (IL-23) orchestrates innate and T cell-dependent colitis; however, the cell populations it acts on to induce intestinal immune pathology are unknown. Here, using Il23r(-/-) T cells, we demonstrated that T cell reactivity to IL-23 was critical for development of intestinal pathology, but not for systemic inflammation. Through direct signaling into T cells, IL-23 drove intestinal T cell proliferation, promoted intestinal Th17 cell accumulation, and enhanced the emergence of an IL-17A(+)IFN-gamma(+) population of T cells. Furthermore, IL-23R signaling in intestinal T cells suppressed the differentiation of Foxp3(+) cells and T cell IL-10 production. Although Il23r(-/-) T cells displayed unimpaired Th1 cell differentiation, these cells showed impaired proliferation and failed to accumulate in the intestine. Together, these results highlight the multiple functions of IL-23 signaling in T cells that contribute to its colitogenic activity.
PMID: 20732640 [PubMed - as supplied by publisher]