Interleukin-23 drives intestinal inflammation through direct activity on T cells.

Journal article

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.

Authors: Ahern, P; Schiering, C; Buonocore, S; McGeachy, M; Cua, D

• Publication status: Published
• Journal: Immunity
• Volume: 33
• Issue: 2
• Pages: 279-288
• Publication date: 2010-08-01
• DOI: 10.1016/j.immuni.2010.08.010
• EISSN: 1097-4180
• ISSN: 1074-7613
• Language: English
• Keywords: Cells, Cultured; T-Lymphocytes; Colitis; Interleukin-23; Mice, Inbred C57BL; Animals; Receptors, Interleukin; Mice; Cell Proliferation; Mice, Knockout