Interleukin 25 Regulates Type 2 Cytokine-dependent Immunity and Limits Chronic Inflammation in the Gastrointestinal Tract

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2006 Apr 12

PMID 16606667

Citations 189

Authors

Alexander M Owyang

Colby Zaph

Emma H Wilson

Katherine J Guild

Terrill Mcclanahan

Hugh R P Miller

Daniel J Cua

Michael Goldschmidt

Christopher A Hunter

Robert A Kastelein

David Artis

Affiliations

Soon will be listed here.

Abstract

The cytokine interleukin (IL) 25 has been implicated in the initiation of type 2 immunity by driving the expression of type 2 cytokines such as IL-5 and IL-13, although its role in the regulation of immunity and infection-induced inflammation is unknown. Here, we identify a dual function for IL-25: first, in promoting type 2 cytokine-dependent immunity to gastrointestinal helminth infection and, second, in limiting proinflammatory cytokine production and chronic intestinal inflammation. Treatment of genetically susceptible mice with exogenous IL-25 promoted type 2 cytokine responses and immunity to Trichuris. IL-25 was constitutively expressed by CD4+ and CD8+ T cells in the gut of mouse strains that are resistant to Trichuris, and IL-25-deficient mice on a genetically resistant background failed to develop a type 2 immune response or eradicate infection. Furthermore, chronically infected IL-25(-/-) mice developed severe infection-induced intestinal inflammation associated with heightened expression of interferon-gamma and IL-17, identifying a role for IL-25 in limiting pathologic inflammation at mucosal sites. Therefore, IL-25 is not only a critical mediator of type 2 immunity, but is also required for the regulation of inflammation in the gastrointestinal tract.

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