IL-33 effects in psoriasis: The induction of pro-inflammatory cytokines via keratinocyte and mast cell activation

Interleukin-33 (IL-33) is the most recent addition to the IL-1 family. It has been shown to function as a ligand for the IL-1 receptor-related protein ST2. Although originally defined as an inducer of Th2-mediated responses, IL-33 was recently found to be involved in arthritis as well as in psoriasis, typical Th1/Th17-mediated diseases. The aim of our study was to investigate the role of IL-33 in psoriasis pathogenesis through its ability to promote inflammation via mast cells (MCs) and keratinocytes (KCs) activation. From in vivo findings, IL-33 resulted elevated in lesional and non lesional skin but not in the serum of psoriasis patients. IL-33 has been shown to be present in the nucleus as well as in the cytoplasm and in the tight junctions of psoriatic KCs; moreover extracellular secretion was induced by TNF-α in immortalized KCs. HaCaT cells, human MCs line (HMC-1) and primary KCs overexpressed IL-33 after TNF-α stimulation, but not after IL-17. TNF-α was able to induce IL-6, MCP-1, VEGF and the addition of IL-33 reinforced these increases. TNF-α and IL-33 combination was also able to induce IL-6 and MCP-1 in ex vivo cultured healthy skin specimens. Our study provides evidence that IL-33 may have a role in psoriasis biology, and that its pathway may involve KCs and MCs.