Epidermal Mammalian Target of Rapamycin Complex 2 Controls Lipid Synthesis and Filaggrin Processing in Epidermal Barrier Formation

August 2019 in “ Journal of Allergy and Clinical Immunology ”

Xiaolei Ding, Sebastian Willenborg, Wilhelm Bloch, Sara A. Wickström, Prerana Wagle, Susanne Brodesser, Axel Roers, Alexander Jaïs, Jens C. Brüning, Michael N. Hall, Markus A. Rüegg, Sabine A. Eming

TLDR mTORC2 is crucial for healthy skin barrier by regulating lipids and filaggrin.

The study investigated the role of mTORC2 in epidermal barrier formation by using RicEKO mice, which had disrupted mTORC2 signaling due to the deletion of Rictor. These mice exhibited impaired epidermal barrier function, characterized by increased transepidermal water loss, dysregulated lipid synthesis, and altered filaggrin processing. Despite a compensatory repair response, structural defects in the stratum corneum and changes in immune cell composition were observed. The findings highlighted mTORC2's critical role in regulating lipid metabolism, filaggrin processing, and immune homeostasis, suggesting potential therapeutic strategies for skin barrier disorders.

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