IL-31-IL-31R interactions negatively regulate type 2 inflammation in the lung

Jacqueline G. Perrigoue, Ji Li, Colby Zaph, Michael Goldschmidt, Phillip Scott, Frederic J. De Sauvage, Edward J. Pearce, Nico Ghilardi, David Artis

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Interleukin (IL) 31Rα (glycoprotein 130-like monocyte receptor and glycoprotein 130-like receptor) heterodimerizes with oncostatin M receptor β to bind IL-31, a cytokine expressed preferentially by CD4+ T helper type 2 (Th2) cells. However, the functions of IL-31-IL-31R signaling in immune regulation remain unknown. Here, we identify a novel role for IL-31R in limiting type 2 inflammation in the lung. After intravenous injection of Schistosoma mansoni eggs, IL-31Rα?/? mice developed severe pulmonary inflammation, characterized by an increase in the area of granulomatous inflammation, increased numbers of resistin-like molecule α+ cells, and enhanced collagen deposition compared to WT counterparts. In vitro, macrophages generated from IL-31Rα?/? mice promoted enhanced ovalbumin-specific CD4+ T cell proliferation and purified naive CD4+ T cells from IL-31Rα?/? mice exhibited enhanced proliferation and expression of Th2 cytokines, identifying a T cell- and macrophage-intrinsic regulatory function for IL-31R signaling. In contrast, the generation of CD4+ T cell-mediated Th1 responses were normal in IL-31Rα?/? mice, suggesting that the regulatory role of IL-31R signaling is limited to type 2 responses. Together, these data implicate IL-31R signaling as a novel negative regulatory pathway that specifically limits type 2 inflammation. JEM

Original languageEnglish
Pages (from-to)481-487
Number of pages7
JournalJournal of Experimental Medicine
Issue number3
Publication statusPublished - 19 Mar 2007
Externally publishedYes

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