Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract

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

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271 Citations (Scopus)

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-γ 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.

Original languageEnglish
Pages (from-to)843-849
Number of pages7
JournalJournal of Experimental Medicine
Volume203
Issue number4
DOIs
Publication statusPublished - 17 Apr 2006
Externally publishedYes

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