title: Interleukin-23 drives intestinal inflammation through direct activity on T cells.
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.
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, England, UK.
authors: Philip P
authors: PP
authors: Ahern
authors: Chris
authors: C
authors: Schiering
authors: Sofia
authors: S
authors: Buonocore
authors: Mandy J
authors: MJ
authors: McGeachy
authors: Dan J
authors: DJ
authors: Cua
authors: Kevin J
authors: KJ
authors: Maloy
authors: Fiona
authors: F
authors: Powrie
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D053759:Interleukin-23 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000172:deficiency / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D053759:Interleukin-23; D018123:Receptors, Interleukin; C528688:interleukin-23 receptor, mouse