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

  • Ahern P
  • Schiering C
  • Buonocore S
 et al. 
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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-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.

Author-supplied keywords

  • Cellimmuno

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Authors

  • daniel cuaMerck Research Labs

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  • Philip P. Ahern

  • Chris Schiering

  • Sofia Buonocore

  • Mandy J. McGeachy

  • Kevin J. Maloy

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