Human Induced Pluripotent Stem Cell–Derived Keratinocyte-Like Cells for Research on Protease-Activated Receptor 2 in Nonhistaminergic Cascades of Atopic Dermatitis

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Keratinocytes are the most abundant cells in the epidermis, and as part of the frontline immunologic defense system, keratinocytes function as a barrier to exogenous attacks. Protease-activated receptor 2 (PAR2) is expressed in human keratinocytes and activated in several inflammatory conditions, such as atopic dermatitis (AD). In this study, we demonstrated the differentiation of human induced pluripotent stem cell into keratinocytes by the improved, robust differentiation procedure and confirmed that human induced pluripotent stem cell-derived keratinocyte-like cells (iKera) express PAR2, which is activated by external addition of the ligand peptide and trypsin. The activation of PAR2 led to the release of calcium from intracellular calcium storage, followed by the release of the proinflammatory cytokine tumor necrosis factor

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