AI Article Synopsis
- The aryl hydrocarbon receptor (AHR) is crucial for maintaining skin cell homeostasis and function as an environmental sensor.
- Upon activation by ligands, AHR influences gene expression by binding to open chromatin, which leads to the swift activation of transcription factors like TFAP2A.
- This study reveals the AHR-TFAP2A pathway's role in promoting keratinocyte differentiation and skin barrier formation, offering new insights for treating skin barrier-related conditions.
Article Abstract
The aryl hydrocarbon receptor (AHR) is an evolutionary conserved environmental sensor identified as an indispensable regulator of epithelial homeostasis and barrier organ function. Molecular signaling cascade and target genes upon AHR activation and their contribution to cell and tissue function are however not fully understood. Multiomics analyses using human skin keratinocytes revealed that upon ligand activation, AHR binds open chromatin to induce expression of transcription factors, for example, TFAP2A, as a swift response to environmental stimuli. The terminal differentiation program, including upregulation of barrier genes, FLG and keratins, was mediated by TFAP2A as a secondary response to AHR activation. The role of AHR-TFAP2A axis in controlling keratinocyte terminal differentiation for proper barrier formation was further confirmed using CRISPR/Cas9 in human epidermal equivalents. Overall, the study provides additional insights into the molecular mechanism behind AHR-mediated barrier function and identifies potential targets for the treatment of skin barrier diseases.
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| http://dx.doi.org/10.1016/j.jid.2024.01.030 | DOI Listing |
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