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

Nature Immunology volume 12, pages 1151–1158 (2011)Cite this article

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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.

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Figure 1: IL-17RE is essential for intestinal immunity to infection with C. rodentium.
Figure 2: IL-17RE is critical for the induction of genes encoding antibacterial molecules during C. rodentium infection.
Figure 3: IL-17RE is required for IL-17C-induced gene expression in colons cultured ex vivo.
Figure 4: IL-17RE is essential for IL-17C-induced gene expression in vivo.
Figure 5: IL-17C binds to IL-17RE and IL-17RA.
Figure 6: IL-17RE is indispensable for IL-17C-induced signaling pathways.
Figure 7: IL-17C is upregulated in CECs after they encounter bacteria.
Figure 8: IL-17C and IL-22 synergistically induce genes encoding antibacterial peptides.

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Acknowledgements

We thank ZymoGenetics for Il17re−/− mice. Supported by the National Natural Science Foundation of China (30930084, 91029708 and 30871298), the 973 program (2010CB529705), the Chinese Academy of Sciences (KSCX2-YW-R-146) and the Science and Technology Commission of Shanghai Municipality (10JC1416600).

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  1. Steven D Levin

    Present address: Present address: Novo Nordisk Inflammation Research Center, Department of Cellular Immunology, Seattle, Washington, USA.,

Authors and Affiliations

  1. The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Xinyang Song, Shu Zhu, Peiqing Shi, Yan Liu, Yufang Shi & Youcun Qian

  2. Department of Immunology, ZymoGenetics, Seattle, Washington, USA

    Steven D Levin

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Contributions

X.S. and Y.Q. designed the experiments and wrote the manuscript; X.S. did most of the experiments; S.Z. and Y.L. helped with the mouse experiments; P.S. helped with the signaling experiments; and S.D.L. and Y.S. provided reagents and technical support.

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Correspondence to Youcun Qian.

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S.D.L. was an employee of ZymoGenetics when these studies were done.

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Song, X., Zhu, S., Shi, P. et al. IL-17RE is the functional receptor for IL-17C and mediates mucosal immunity to infection with intestinal pathogens. Nat Immunol 12, 1151–1158 (2011). https://doi.org/10.1038/ni.2155

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