Immune functions and recruitment of plasmacytoid dendritic cells in psoriasis

Abstract

Psoriasis is one of the most common chronic T cell-mediated diseases in humans. Among the most proximal event in the innate immunity cascade driving psoriatic inflammation is the secretion of type I IFN by activated plasmacytoid dendritic cells (pDC), a special DC subset strategically positioned in pre-psoriatic symptomless skin. There is an IFN-alpha signature in primary psoriatic plaques, and blocking of type I IFN signalling can prevent the expansion of pathogenetic T cells and development of psoriatic phenotype. Recently, we have demonstrated that pDC infiltration in psoriatic skin correlates with the expression of markers typical of early phases of psoriasis, whereas it is almost absent in long-lasting lesions. Importantly, pDC recruitment in psoriatic skin is strictly associated with the chemerin/ChemR23 axis, and is temporally active during psoriatic plaque development. Pro-chemerin is produced primarily by dermal fibroblasts, but also by mast cells and endothelial cells. Once secreted, it can be activated by enzymes produced by neutrophils and mast cells, which infiltrate early psoriasis lesions. These findings propose the chemerin/ChemR23 axis as a potential novel therapeutic target in psoriasis.