Schematic representation of the potential pro-inflammatory role of IL-33 in normal skin and in skin inflammation (atopic dermatitis and psoriasis). Damage to the skin such as by scratching in response to an allergen and inflammation lead to cell necrosis and release of biologically active IL-33. IL-33 can interact with its receptor ST2L on a number of cell types within the skin, including resident skin cells and infiltrating immune cells. IL-33 may drive dendritic cell (DC) mediated polarization of naïve CD4+ T cells towards a Th2 phenotype and the production of cytokines such as IL-5, IL-10 and IL-13. IL-33 can also potently activate innate immune cells such as mast cells (MC) leading to release of biologically active mediators such as VEGF, histamine and prostaglandin E2 (PGE2). IL-33 can also lead to production of the chemokine KC, thus recruiting neutrophils (N). An increase in Th17 cells and related cytokines IL-17/22 may be driven by IL-33 stimulation of IL-1 and IL-6 production. Furthermore, IL-33 mediated production of VEGF may drive angiogenesis and skin remodeling.