Psoriasis is widely regarded as an inflammatory T-cell-mediated disorder, where the hyperproliferation and disturbed maturation of the keratinocytes (KCs) are believed to be driven by Th1- and Th17-associated cytokines and chemokines. Although recent genetic advances suggest that both immune and epidermal components contribute to disease susceptibility, the role of KCs in the formation of the psoriatic lesion has received less attention. We applied flow cytometry on KCs from lesional and non-lesional epidermis and observed an overall increase in the expression of established stemness markers. We found a reduced percentage of cells positive for the early differentiation marker, cytokeratin 10 (K10), while the upregulation of stemness markers was more pronounced in the K10+ cells. We hypothesized that stimuli present in the psoriatic microenvironment would be a contributing cause for the cellular immaturity. Indeed, treatment with IL-17 and IL-22 induced a similar expression pattern of stem cell markers in normal KCs with increase in CD44, p63 and CD29 and a decrease in K10. Furthermore, IL-17 and IL-22 increased the colony-forming efficiency and long-term proliferative capacity, reflecting increased stem cell-like characteristics in the KC population. Like the reduced size observed in the lesion-derived psoriatic KCs, the size of the KCs decreased after treatment with IL-17 and IL-22. Moreover, when compared with normal KCs seeded at colony density for 10 days, psoriatic KCs formed a strikingly larger number of colonies of larger size. 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.

IL-17 and IL-22 promote keratinocyte stemness in the germinative compartment in psoriasis