AP-2α/AP-2β Transcription Factors Are Key Regulators of Epidermal Homeostasis

The study reveals that AP-2α and AP-2β transcription factors are crucial for maintaining epidermal homeostasis in adult skin. AP-2α is the primary AP-2 family member in adult epidermis, with AP-2β also present. The research shows that AP-2α can compensate for the loss of AP-2β in keratinocytes, but the loss of AP-2α disrupts terminal keratinocyte differentiation and hair morphogenesis. When both AP-2α and AP-2β are absent, there are more severe skin and hair abnormalities, which are followed by a progressive neutrophilic skin inflammation. Transcriptomic analysis indicates that the absence of AP-2α or both AP-2α and AP-2β in keratinocytes leads to a terminal differentiation defect, with increased expression of alarmin keratins and immune pathway regulators. The study suggests that the loss of AP-2α-dependent gene expression of CXCL14 and KRT15 may be an early event leading to skin inflammation, underscoring the importance of AP-2α/AP-2β in skin health.