The IL-20 subfamily of cytokines — from host defence to tissue homeostasis

Key Points Members of the interleukin-20 (IL-20) subfamily of cytokines are mainly produced by haematopoietic cells but these cytokines signal through receptors that are primarily expressed on epithelial tissues. These cytokines facilitate the communication between leukocytes and epithelial cells, and thereby enhance innate defence mechanisms and tissue repair processes at epithelial surfaces. IL-20 subfamily cytokines stimulate the proliferation of epithelial cells and also their production of antimicrobial proteins, and pro-inflammatory cytokines and chemokines. All of these functions strengthen epithelial barrier function. IL-22 is indispensable for host defence during infection with extracellular pathogens such as Citrobacter rodentium , Klebsiella pneumoniae and yeast. The roles of the other IL-20 subfamily cytokines during infection are still mostly undefined. IL-20 subfamily cytokines are induced during wound healing in the skin and contribute to several stages of the wound-healing process, including inflammation, angiogenesis, re-epithelialization and remodelling. IL-20 subfamily cytokines are not tumorigenic per se, but they can have both tumour-promoting and tumour-suppressive effects on tumours of epithelial origin, depending on the tumour stage and the local inflammatory environment. Emerging data suggest that IL-22 — and presumably other IL-20 subfamily cytokines — can regulate metabolic processes such as lipid metabolism. IL-22 can also ameliorate metabolic syndrome by enhancing intestinal mucosal immunity and reducing chronic systemic inflammation. This Review describes the biology of the interleukin-20 (IL-20) subfamily of cytokines. The authors detail the cellular sources and targets of these cytokines, and explain their key roles in promoting immunity to infections and driving tissue repair. They also discuss the emerging roles for IL-20 subfamily cytokines in metabolism and tumour immunology. The interleukin-20 (IL-20) subfamily of cytokines comprises IL-19, IL-20, IL-22, IL-24 and IL-26. These cytokines are all members of the larger IL-10 family, but have been grouped together to form the IL-20 subfamily based on their usage of common receptor subunits and similarities in their target-cell profiles and biological functions. Members of the IL-20 subfamily facilitate the communication between leukocytes and epithelial cells, thereby enhancing innate defence mechanisms and tissue repair processes at epithelial surfaces. In this Review, we