Abstract
Interleukin 17 receptor E (IL-17RE) is an orphan receptor of the IL-17 receptor family. Here we show that IL-17RE is a receptor specific to IL-17C and has an essential role in host mucosal defense against infection. IL-17C activated downstream signaling through IL-17RE-IL-17RA complex for the induction of genes encoding antibacterial peptides as well as proinflammatory molecules. IL-17C was upregulated in colon epithelial cells during infection with Citrobacter rodentium and acted in synergy with IL-22 to induce the expression of antibacterial peptides in colon epithelial cells. Loss of IL-17C-mediated signaling in IL-17RE-deficient mice led to lower expression of genes encoding antibacterial molecules, greater bacterial burden and early mortality during infection. Together our data identify IL-17RE as a receptor of IL-17C that regulates early innate immunity to intestinal pathogens.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antimicrobial Cationic Peptides / genetics
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Antimicrobial Cationic Peptides / immunology
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Cell Line
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Citrobacter rodentium
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Colon / immunology
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Colon / metabolism
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Enterobacteriaceae Infections / genetics
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Enterobacteriaceae Infections / immunology*
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Enterobacteriaceae Infections / microbiology
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Gene Expression Regulation
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HEK293 Cells
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HT29 Cells
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Humans
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Immunity, Mucosal / genetics
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Immunity, Mucosal / immunology*
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Interleukin-17 / metabolism*
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Interleukin-22
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Interleukins / metabolism
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Intestinal Mucosa / immunology*
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Intestinal Mucosa / microbiology
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Intestinal Mucosa / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Interleukin-17 / genetics
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Receptors, Interleukin-17 / metabolism*
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Signal Transduction
Substances
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Antimicrobial Cationic Peptides
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IL17RA protein, human
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Interleukin-17
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Interleukins
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Receptors, Interleukin-17