Interleukin-23 Drives Intestinal Inflammation through Direct Activity on T Cells

Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, England, UK.
Immunity (Impact Factor: 19.75). 08/2010; 33(2):279-88. DOI: 10.1016/j.immuni.2010.08.010
Source: PubMed

ABSTRACT 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.


Available from: Chris Schiering, Nov 20, 2014
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