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IL‐27‐IL‐27R interactions regulate homeostasis of the TH17 pool and limit intestinal inflammation
Author(s) -
Troy Amy E,
Saris Christiaan J M,
Hunter Christopher A,
Artis David
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1069.7
Subject(s) - inflammation , immunology , innate immune system , colitis , lamina propria , biology , immune system , innate lymphoid cell , epithelium , genetics
IL‐27 can suppress production of IL‐17 by T H 17 cells both in vitro and in vivo . While T H 17 cells are abundant in the lamina propria of the intestine under steady‐state conditions, whether IL‐27 regulates homeostasis of these cells is unknown. Using IL‐27R −/− mice, we demonstrate that IL‐27‐IL‐27R interactions limit the size of the intestinal T H 17 pool. To determine whether IL‐27 could limit intestinal T H 17 responses under inflammatory conditions, IL‐27R −/− mice were exposed to DSS in an acute model of colitis. IL‐27R −/− mice exhibited significantly increased CD4‐derived IL‐17 and developed rapid and severe colitis compared to wild‐type controls. To address the role of IL‐27‐IL‐27R interaction on innate immune cells, Rag −/− /IL‐27R −/− mice were exposed to DSS. These mice exhibited increased severity of disease compared to Rag −/− controls, indicating that IL‐27‐IL‐27R interactions can regulate innate cell function during DSS colitis. rIL‐27 decreased transcription of pro‐inflammatory cytokines by activated neutrophils in vitro ; this may contribute to its ability to inhibit innate cell–driven inflammation. Together these results identify a role for IL‐27‐IL‐27R interactions in controlling the size of the intestinal T H 17 cell pool under steady‐state conditions and in limiting intestinal inflammation through its effects on innate and adaptive immune cells.