IL-33 and keratinocytes: a trait d'union in innate immunity mechanisms of psoriasis.

Abstract

IL-33 is a pro-inflammatory cytokine recently identified as a ligand for the orphan receptor ST2. IL-33 constitutive nuclear expression has been found in cells of tissues exposed to the environment. Moreover endothelial cells have been shown to abundantly express IL-33. Many of the inflammatory effects of IL-33 define its ability to induce Th2-type mediated responses but recently IL-33 was found to have a pro-inflammatory role in arthritis, which is Th1 and/or Th17 mediated. It can be hypothesized that IL-33 has a pro-inflammatory role in psoriasis too. In the present study we aimed to assess the role of IL-33 in psoriasis, investigating its property to promote inflammation via MC and KC activation. Here we report that IL-33 is elevated in the skin of psoriasis patients. Furthermore, IL-33 upregulates IL-4 and IL-13 and is able to induce a higher increase of MCP-1 and VEGF respect to TNF-α in MCs. In presence of TNF-α, IL-33 induces MCP-1 and IL-6, whereas in association with IL-17, is able to induce IL-20 in KCs. In conclusion, our study provides evidence that IL-33 is involved in psoriasis biology. Furthermore, our results reinforce the IL-33 activity in driving Th1 response too, contributing to the maintenance of psoriasis pathogenesis.