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Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22

Abstract

The maintenance of barrier function at exposed surfaces of the mammalian body is essential for limiting exposure to environmental stimuli, preventing systemic dissemination of commensal and pathogenic microbes and retaining normal homeostasis of the entire body. Indeed, dysregulated barrier function is associated with many infectious and inflammatory diseases, including psoriasis, influenza, inflammatory bowel disease and human immunodeficiency virus, which collectively afflict millions of people worldwide. Studies have shown that interleukin 22 (IL-22) is expressed at barrier surfaces and that its expression is dysregulated in certain human diseases, which suggests a critical role in the maintenance of normal barrier homeostasis. Consistent with that, studies of mouse model systems have identified a critical role for signaling by IL-22 through its receptor (IL-22R) in the promotion of antimicrobial immunity, inflammation and tissue repair at barrier surfaces. In this review we will discuss how the expression of IL-22 and IL-22R is regulated, the functions of the IL-22–IL-22R pathway in regulating immunity, inflammation and tissue homeostasis, and the therapeutic potential of targeting this pathway in human disease.

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Figure 1: Functional consequences of IL-22–IL-22R signaling at barrier surfaces.
Figure 2: Regulation, function and lineage relationships of IL-22-producing ILCs.
Figure 3: Differentiation, regulation and function of IL-22-producing T cell populations.

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Acknowledgements

We thank all members of the Artis laboratory, in particular L.A. Monticelli, M.G. Nair and S.A. Saenz, for discussions and critical reading of the manuscript. Supported by the US National Institutes of Health (AI61570, AI74878, AI087990 and AI083480 to D.A., and T32AI007532-08 to G.F.S.), the Burroughs Wellcome Fund (D.A.) and the University of Pennsylvania (Veterinary Center of Infectious Diseases, Penn Genome Frontiers Institute and University Research Fund to D.A.).

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L.A.F. is employed by Pfizer.

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Sonnenberg, G., Fouser, L. & Artis, D. Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nat Immunol 12, 383–390 (2011). https://doi.org/10.1038/ni.2025

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