| First Author | Zhang H | Year | 2024 |
| Journal | J Invest Dermatol | Volume | 144 |
| Issue | 7 | Pages | 1505-1521.e12 |
| PubMed ID | 38237728 | Mgi Jnum | J:361036 |
| Mgi Id | MGI:7855454 | Doi | 10.1016/j.jid.2023.12.017 |
| Citation | Zhang H, et al. (2024) AP-2alpha/AP-2beta Transcription Factors Are Key Regulators of Epidermal Homeostasis. J Invest Dermatol 144(7):1505-1521.e12 |
| abstractText | AP-2 transcription factors regulate ectodermal development, but their roles in epidermal homeostasis in adult skin are unknown. We find that AP-2alpha is the predominant AP-2 family member in adult epidermis, followed by AP-2beta. Through inactivation of AP-2alpha, AP-2beta, or both in keratinocytes, we assessed the effects of a gradient of epidermal AP-2 activity on skin function. We find that (i) loss of AP-2beta in keratinocytes is compensated for by AP-2alpha, (ii) loss of AP-2alpha impairs terminal keratinocyte differentiation and hair morphogenesis, and (iii) the combined loss of AP-2alpha/AP-2beta results in more severe skin and hair abnormalities. Keratinocyte differentiation defects precede progressive neutrophilic skin inflammation. Inducible inactivation of AP-2alpha/AP-2beta in the adult phenocopies these manifestations. Transcriptomic analyses of epidermis lacking AP-2alpha or AP-2alpha/AP-2beta in keratinocytes demonstrate a terminal keratinocyte differentiation defect with upregulation of alarmin keratins and of several immune pathway regulators. Moreover, our analyses suggest a key role of reduced AP-2alpha-dependent gene expression of CXCL14 and the keratin 15 gene K15 as an early pathogenic event toward the manifestation of skin inflammation. Thus, AP-2alpha and AP-2beta are critical regulators of epidermal homeostasis in adult skin. |
