Transcription Factor Regulation of Epidermal Differentiation and Inflammation

The epidermis is far more than a mechanical shield; it is a dynamic immunological interface whose structural integrity and immune homeostasis are co-regulated by interconnected transcriptional networks. This review examines how epidermal differentiation promoting transcription factors coordinate terminal keratinocyte maturation, skin barrier formation, immune suppression, lipid metabolism, and tissue repair. In particular, Zinc finger protein 750 (ZNF750), grainyhead-like transcription factor 3 (GRHL3), and ovo-like transcriptional repressor 1 (OVOL1) integrate epidermal differentiation with the suppression of inflammatory signaling by regulating lipid metabolism, innate immune sensors, stress-response pathways, and environmentally responsive transcriptional programs. Disruption of these regulatory nodes impairs barrier integrity, amplifies inflammatory signaling, and predisposes to chronic skin diseases, including psoriasis and atopic dermatitis.