Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis

Izcue, A., Hue, S., Buonocore, S., Arancibia-Cárcamo, C. V., Ahern, P. P., Iwakura, Y., Maloy, K. J. and Powrie, F. (2008) Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis. Immunity, 28(4), pp. 559-570. (doi: 10.1016/j.immuni.2008.02.019) (PMID:18400195) (PMCID:PMC2292821)

Abstract

Interleukin-23 (IL-23) is an inflammatory cytokine that plays a key role in the pathogenesis of several autoimmune and inflammatory diseases. It orchestrates innate and T cell-mediated inflammatory pathways and can promote T helper 17 (Th17) cell responses. Utilizing a T cell transfer model, we showed that IL-23-dependent colitis did not require IL-17 secretion by T cells. Furthermore, IL-23-independent intestinal inflammation could develop if immunosuppressive pathways were reduced. The frequency of naive T cell-derived Foxp3+ cells in the colon increased in the absence of IL-23, indicating a role for IL-23 in controlling regulatory T cell induction. Foxp3-deficient T cells induced colitis when transferred into recipients lacking IL-23p19, showing that IL-23 was not essential for intestinal inflammation in the absence of Foxp3. Taken together, our data indicate that overriding immunosuppressive pathways is an important function of IL-23 in the intestine and could influence not only Th17 cell activity but also other types of immune responses.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Maloy, Professor Kevin
• Authors: Izcue, A., Hue, S., Buonocore, S., Arancibia-Cárcamo, C. V., Ahern, P. P., Iwakura, Y., 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: 10 April 2008
• Copyright Holders: Copyright © 2008 Elsevier Inc.
• First Published: First published in Immunity 28(4): 559-570
• Publisher Policy: Reproduced under a Creative Commons License