IL-27 regulates homeostasis of the intestinal CD4+ effector T cell pool and limits intestinal inflammation in a murine model of colitis

Amy E. Troy, Colby Zaph, Yurong Du, Betsy C. Taylor, Katherine J. Guild, Christopher A. Hunter, Christiaan J M Saris, David Artis

Research output: Contribution to journalArticleResearchpeer-review

53 Citations (Scopus)

Abstract

IL-27 limits CD4+ TH17 cell development in vitro and during inflammatory responses in the CNS. However, whether IL-27-IL-27R interactions regulate the homeostasis or function of CD4+ T cell populations in the intestine is unknown. To test this, we examined CD4 + T cell populations in the intestine of wild-type and IL-27R -/- mice. Naive IL-27R-/- mice exhibited a selective decrease in the frequency of IFN-γ producing CD4+ T H1 cells and an increase in the frequency of TH17 cells in gut-associated lymphoid tissues. Associated with elevated expression of IL-17A, IL-27R-/- mice exhibited earlier onset and significantly increased severity of clinical disease compared with wild-type controls in a murine model of intestinal inflammation. Rag-/-/IL-27R-/- mice were also more susceptible than Rag-/- mice to development of dextran sodium sulfate-induced intestinal inflammation, indicating an additional role for IL-27-IL-27R in the regulation of innate immune cell function. Consistent with this, IL-27 inhibited proinflammatory cytokine production by activated neutrophils. Collectively, these data identify a role for IL-27-IL-27R interaction in controlling the homeostasis of the intestinal T cell pool and in limiting intestinal inflammation through regulation of innate and adaptive immune cell function.

Original languageEnglish
Pages (from-to)2037-2044
Number of pages8
JournalJournal of Immunology
Volume183
Issue number3
DOIs
Publication statusPublished - 1 Aug 2009
Externally publishedYes

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