IL-1β mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4+Th17 cells

Coccia, M., Harrison, O. J., Schiering, C., Asquith, M. J., Becher, B., Powrie, F. and Maloy, K. J. (2012) IL-1β mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4+Th17 cells. Journal of Experimental Medicine, 209(9), pp. 1595-1609. (doi: 10.1084/jem.20111453) (PMID:22891275) (PMCID:PMC3428945)

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Abstract

Although very high levels of interleukin (IL)-1β are present in the intestines of patients suffering from inflammatory bowel diseases (IBD), little is known about the contribution of IL-1β to intestinal pathology. Here, we used two complementary models of chronic intestinal inflammation to address the role of IL-1β in driving innate and adaptive pathology in the intestine. We show that IL-1β promotes innate immune pathology in Helicobacter hepaticus–triggered intestinal inflammation by augmenting the recruitment of granulocytes and the accumulation and activation of innate lymphoid cells (ILCs). Using a T cell transfer colitis model, we demonstrate a key role for T cell–specific IL-1 receptor (IL-1R) signals in the accumulation and survival of pathogenic CD4+ T cells in the colon. Furthermore, we show that IL-1β promotes Th17 responses from CD4+ T cells and ILCs in the intestine, and we describe synergistic interactions between IL-1β and IL-23 signals that sustain innate and adaptive inflammatory responses in the gut. These data identify multiple mechanisms through which IL-1β promotes intestinal pathology and suggest that targeting IL-1β may represent a useful therapeutic approach in IBD.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maloy, Professor Kevin
Authors: Coccia, M., Harrison, O. J., Schiering, C., Asquith, M. J., Becher, B., Powrie, F., and Maloy, K. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Experimental Medicine
Publisher:Rockefeller University Press
ISSN:0022-1007
ISSN (Online):1540-9538
Published Online:13 August 2012

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