Journal
NATURE IMMUNOLOGY
Volume 12, Issue 12, Pages 1151-UPublisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2155
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Funding
- National Natural Science Foundation of China [30930084, 91029708, 30871298]
- 973 program [2010CB529705]
- Chinese Academy of Sciences [KSCX2-YW-R-146]
- Science and Technology Commission of Shanghai Municipality [10JC1416600]
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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.
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