IL-17RE is the functional receptor for IL-17C and mediates mucosal immunity to infection with intestinal pathogens

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.