IL-17 and IL-22 Promote Keratinocyte Stemness in the Germinative Compartment in Psoriasis

Abstract

Psoriasis is an inflammatory skin disorder characterized by the hyperproliferation of basal epidermal cells. It is regarded as T-cell mediated, but the role of keratinocytes (KCs) in the disease pathogenesis has reemerged, with genetic studies identifying KC-associated genes. We applied flow cytometry on KCs from lesional and nonlesional epidermis to characterize the phenotype in the germinative compartment in psoriasis, and we observed an overall increase in the stemness markers CD29 (2.4-fold), CD44 (2.9-fold), CD49f (2.8-fold), and p63 (1.4-fold). We found a reduced percentage of cells positive for the early differentiation marker cytokeratin 10 and a greater fraction of CD29+ and involucrin+ cells in the psoriasis KCs than in nonlesional KCs. The up-regulation of stemness markers was more pronounced in the K10+ cells. Furthermore, the psoriasis cells were smaller, indicating increased proliferation. Treatment with IL-17 and IL-22 induced a similar expression pattern of an up-regulation of p63, CD44, and CD29 in normal KCs and increased the colony-forming efficiency and long-term proliferative capacity, reflecting increased stem cell-like characteristics in the KC population. These data suggest that IL-17 and IL-22 link the inflammatory response to the immature differentiation and epithelial regeneration by acting directly on KCs to promote cell stemness.