Psoriasis-like inflammation induces mitochondrial function and structure changes in human keratinocytes and fibroblasts

Abstract

AbstractMitochondrial structural and functional changes accompany psoriasis; however, the mitochondrial response to psoriatic inflammation in keratinocytes and fibroblasts has not been studied. Here, we investigate the effect of psoriasis-like inflammation (PLI) induced by cytokine cocktail (IL-17, IL-22, TNF-α) on mitochondrial network morphology and function in living cultured keratinocytes (HaCaT) and fibroblasts (BJ-5ta). In both skin cell types, PLI triggered expression of psoriasis-related SKALP/Elafin and high amounts of cytokines (IL-1, IL-6), interferons (IFN-α, IFN-β, IFN-γ), and chemokines (CCL5, CXCL8), accompanied by mitochondrial ROS production, network fragmentation, swelling, and cristae disassembly. STED nanoscopy revealed that the mitochondrial cristae are disappearing in response to PLI, with the process starting faster and being more pronounced in keratinocytes than in fibroblasts. Moreover, in keratinocytes, PLI leads to mitochondrial respiration suppression and elimination of the organelles. These findings of cell-specific mitochondrial responses may guide future investigations into new pharmacological targets for managing psoriasis.Abstract Figure