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Unlocking Skin's Secret Defender: AHR's Role in Barrier Formation

The Aryl Hydrocarbon Receptor (AHR), as an evolutionary conserved environmental sensor transferring signals into nuclei in many different tissues, plays an important role in the formation of the skin epidermis. However, the exact molecular signalling cascades and target genes upon AHR activation for controlling the integrity of the epidermis are not fully understood, hampering further therapeutic development using AHR as a target.

Researchers Jos Smits and Jieqiong Qu investigated and uncovered this control mechanism that AHR regulates epidermal barrier function via transient activation of Transcription Factor AP-2 alpha (TFAP2A). The research groups led by Ellen van den Bogaard of the Department of Dermatology (Radboudumc) and Jo Huiqing Zhou of the Department of Molecular Developmental Biology (RIMLS-Science, Radboud university) published the results in a recent publication in Journal of Investigative Dermatology.

Through multidisciplinary teamwork, investigators combined advanced multi-omics technologies (RNA-sequencing, AHR-specific and H3K27ac-specific ChIP-sequencing) with epidermal keratinocyte cell models, epidermal organoids and biophysical measurements. They demonstrated that, upon AHR activation, the AHR transiently activates expression of a set of key transcription factors (e.g., TFAP2A) that initiate the terminal epidermal differentiation program. By CRISPR/Cas9 technologies, the role of the AHR-TFAP2A axis in controlling keratinocyte terminal differentiation and skin barrier function was confirmed. Overall, the study provides insights into the molecular mechanisms behind AHR-mediated barrier function and identifies potential targets and alternative routes for the treatment of common diseases showcasing aberrant differentiation and barrier dysfunction.

Literature reference

The aryl hydrocarbon receptor regulates epidermal differentiation through transient activation of TFAP2A. Journal of Investigative Dermatology (2024). DOI: 10.1016/j.jid.2024.01.030. Jos P.H. Smits, Jieqiong Qu, Felicitas Pardow, Noa J.M. van den Brink, Diana Rodijk-Olthuis, Ivonne M.J.J. van Vlijmen-Willems, Simon J. van Heeringen, Patrick L.J.M. Zeeuwen, Joost Schalkwijk, Huiqing Zhou, Ellen H. van den Bogaard.

Contact information

For more information, please get in touch with Jo Huiqing Zhou.

Health & Healthcare