Ovol1/2 loss‐induced epidermal defects elicit skin immune activation and alter global metabolism

Skin epidermis constitutes the outer permeability barrier that protects the body from dehydration, heat loss, and myriad external assaults. Mechanisms that maintain barrier integrity in constantly challenged adult skin and how epidermal dysregulation shapes the local immune microenvironment and whol...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:EMBO reports 2023-07, Vol.24 (7), p.e56214-n/a
Hauptverfasser: Dragan, Morgan, Chen, Zeyu, Li, Yumei, Le, Johnny, Sun, Peng, Haensel, Daniel, Sureshchandra, Suhas, Pham, Anh, Lu, Eddie, Pham, Katherine Thanh, Verlande, Amandine, Vu, Remy, Gutierrez, Guadalupe, Li, Wei, Jang, Cholsoon, Masri, Selma, Dai, Xing
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Skin epidermis constitutes the outer permeability barrier that protects the body from dehydration, heat loss, and myriad external assaults. Mechanisms that maintain barrier integrity in constantly challenged adult skin and how epidermal dysregulation shapes the local immune microenvironment and whole‐body metabolism remain poorly understood. Here, we demonstrate that inducible and simultaneous ablation of transcription factor‐encoding Ovol1 and Ovol2 in adult epidermis results in barrier dysregulation through impacting epithelial‐mesenchymal plasticity and inflammatory gene expression. We find that aberrant skin immune activation then ensues, featuring Langerhans cell mobilization and T cell responses, and leading to elevated levels of secreted inflammatory factors in circulation. Finally, we identify failure to gain body weight and accumulate body fat as long‐term consequences of epidermal‐specific Ovol1/2 loss and show that these global metabolic changes along with the skin barrier/immune defects are partially rescued by immunosuppressant dexamethasone. Collectively, our study reveals key regulators of adult barrier maintenance and suggests a causal connection between epidermal dysregulation and whole‐body metabolism that is in part mediated through aberrant immune activation. Synopsis Skin epidermal‐specific loss of Ovol1 and Ovol2 transcription factors also causes local immune activation and whole‐body metabolic changes. These defects are partially rescued by administration of the immunosuppressant dexamethasone. EMT‐suppressing transcription factors Ovol1 and Ovol2 are required for epidermal barrier maintenance in adult skin. Ovol1/2 loss‐induced epidermal dysregulation elicits aberrant immune activation and increased production of inflammatory factors. Ovol1/2 perturbation in epidermis results in a failure to gain body weight and accumulate body fat. Partial rescue by dexamethasone implicates connections among epidermal and immune homeostasis, and global metabolism. Graphical Abstract Skin epidermal‐specific loss of Ovol1 and Ovol2 transcription factors also causes local immune activation and whole‐body metabolic changes. These defects are partially rescued by administration of the immunosuppressant dexamethasone.
ISSN:1469-221X
1469-3178
1469-3178
DOI:10.15252/embr.202256214