Interleukin-22 promotes fibroblast- mediated wound repair in the skin

Skin wound repair requires complex and highly coordinated interactions between keratinocytes, fibroblasts and immune cells to restore the epidermal barrier and tissue architecture after acute injury. The cytokine interleukin-22 (IL-22) mediates unidirectional signaling from immune cells to epithelial cells during injury of peripheral tissues such as the liver and colon, where IL-22 causes epithelial cells to produce anti-bacterial proteins, express mucins, and enhance epithelial regeneration. In this study, we use IL-22(−/−) mice to investigate the in vivo role for IL-22 in acute skin wounding. We find that IL-22(−/−) mice display major defects in the skin’s dermal compartment after full thickness wounding. We find that IL-22 signaling is active in fibroblasts using in vitro assays with primary fibroblasts and that IL-22 directs extracellular matrix (ECM) gene expression as well as myofibroblast differentiation both in vitro and in vivo. These data define roles of IL-22 beyond epithelial crosstalk, and suggest that IL-22 plays a previously unidentified role in skin repair by mediating interactions between immune cells and fibroblasts.