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Members of the IL-20 cytokine subfamily serve as crucial links between the immune system and epithelial tissues, as their receptors are predominantly expressed on epithelial cells and they are primarily produced by immune cells. IL-20 is a pro-inflammatory and angiogenic cytokine mainly secreted by monocytes and skin keratinocytes. It plays significant roles in immune responses, regulation of inflammation, hematopoiesis, and the differentiation of epidermal and keratinocyte cells.
IL-20 enhances tissue remodeling and wound healing, helping to restore the homeostasis of epithelial layers during infections and inflammation. It affects neutrophil functions by inhibiting phagocytosis, granule exocytosis, and migration. The cytokine exerts its effects through two receptor complexes: the type I IL-20 receptor (IL20RA and IL20RB) and the type II receptor complex (IL22RA1 and IL20RB). It activates various signaling pathways, including the phosphorylation of JAK2 and STAT5, and also engages AKT and ERK1/2 kinases. Additionally, in keratinocytes, it can activate STAT3 in a JAK2, ERK1/2, and p38 MAPK-dependent manner.