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-γ+ 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. © 2010 Elsevier Inc.
CITATION STYLE
Ahern, P. P., Schiering, C., Buonocore, S., McGeachy, M. J., Cua, D. J., Maloy, K. J., & Powrie, F. (2010). Interleukin-23 Drives Intestinal Inflammation through Direct Activity on T Cells. Immunity, 33(2), 279–288. https://doi.org/10.1016/j.immuni.2010.08.010
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