[PDF][PDF] Interleukin-23 drives intestinal inflammation through direct activity on T cells

PP Ahern, C Schiering, S Buonocore, MJ McGeachy… - Immunity, 2010 - cell.com
PP Ahern, C Schiering, S Buonocore, MJ McGeachy, DJ Cua, KJ Maloy, F Powrie
Immunity, 2010cell.com
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 …
Summary
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.
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