IL-31-IL-31R interactions limit the magnitude of Th2 cytokine-dependent immunity and inflammation following intestinal helminth infection

Jacqueline G. Perrigoue, Colby Zaph, Katherine Guild, Yurong Du, David Artis

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IL-31 is a recently identified cytokine made predominantly by CD4 + Th2 cells and its receptor, IL-31R, is expressed by a number of cell types including monocytes, epithelial cells, and T cells. Originally identified as a potential mediator of inflammation in the skin, we recently reported a novel function for endogenous IL-31R interactions in limiting type 2 inflammation in the lung. However, whether IL-31-IL-31R interactions regulate immunity or inflammation at other mucosal sites, such as the gut, is unknown. In this study, we report a regulatory role for IL-31-IL-31R interactions in the intestine following infection with the gastrointestinal helminth Trichuris muris, immunity to which is critically dependent on CD4+ Th2 cells that produce IL-4 and IL-13. IL-31Rα was constitutively expressed in the colon and exposure to Trichuris induced the expression of IL-31 in CD4 + T cells. In response to Trichuris infection, IL-31Rα -/- mice exhibited increased Th2 cytokine responses in the mesenteric lymph nodes and elevated serum IgE and IgG1 levels compared with wild type mice. IL-31Rα-/- mice also displayed enhanced goblet cell hyperplasia and a marked increase in secretion of goblet cell-derived resistin-like molecule β into the intestinal lumen. Consistent with their exacerbated type 2 inflammatory responses, IL-31Rα-/- mice exhibited accelerated expulsion of Trichuris with significantly decreased worm burdens compared with their wild type counterparts early following infection. Collectively, these data provide the first evidence of a function for IL-31-IL-31R interactions in limiting the magnitude of type 2 inflammatory responses within the intestine.

Original languageEnglish
Pages (from-to)6088-6094
Number of pages7
JournalJournal of Immunology
Issue number10
Publication statusPublished - 15 May 2009
Externally publishedYes

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