IL-33 is secreted by psoriatic keratinocytes and induces pro-inflammatory cytokines via keratinocyte and mast cell activation

IL-33 is a novel pro-inflammatory cytokine and ligand for the orphan receptor ST2. Although originally defined as an inducer of Th2-mediated responses, IL-33 was recently found to be involved in arthritis, a Th1/Th17-mediated disease. Here, we assessed the ability of IL-33 to promote inflammation via mast cells (MCs) and keratinocytes (KCs) activation in psoriasis. IL-33 resulted elevated in the skin but not in the serum of psoriasis patients. IL-33 was secreted by psoriasis KCs and HaCaT cells after TNF-alpha stimulation. In HMC-1, TNF-alpha, but not IL-17, could induce a robust increase in IL-33 expression. In HaCaT cells, TNF-alpha was able to induce IL-6, MCP-1 and VEGF, and the addition of IL-33 reinforced these increases. TNF-alpha + IL-33 combination showed similar results in primary KCs and ex vivo skin organ culture. In conclusion, our study suggests that IL-33 may be involved in psoriasis biology via MCs and KCs.