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

Ahern, P. P., Schiering, C., Buonocore, S., McGeachy, M. J., Cua, D. J., Maloy, K. J. and Powrie, F. (2010) Interleukin-23 drives intestinal inflammation through direct activity on T cells. Immunity, 33(2), pp. 279-288. (doi: 10.1016/j.immuni.2010.08.010) (PMID:20732640) (PMCID:PMC3078329)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Maloy, Professor Kevin
• Authors: Ahern, P. P., Schiering, C., Buonocore, S., McGeachy, M. J., Cua, D. J., Maloy, K. J., and Powrie, F.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Immunity
• Publisher: Elsevier (Cell Press)
• ISSN: 1074-7613
• ISSN (Online): 1097-4180
• Published Online: 26 August 2010
• Copyright Holders: Copyright © 2010 Elsevier Inc.
• First Published: First published in Immunity 33(2): 279-288
• Publisher Policy: Reproduced under a Creative Commons License