A commensally regulated immune rheostat fine-tunes skin barrier fitness
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Updated: Oct 31, 2026
Preparation of Single-cell Suspensions for Cytofluorimetric Analysis from Different Mouse Skin Regions
Published on: April 20, 2016
Anita Gola1, Rohith Srinivas1, Elias G Rodig1
1Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA.
Abstract:
At the skin's surface, the epidermis must balance stem cell renewal with barrier maintenance to withstand environmental stress and shield against pathogens. In this study, we identify a microbial-immune-epithelial feedback mechanism that integrates environmental information into stem cell regulation in mice. Specifically, we show that Langerhans cells (LCs), an intraepithelial macrophage population, orchestrate this circuit by producing prostaglandin E2, which restrains stem cell proliferation, promotes epidermal differentiation, and maintains barrier integrity during homeostasis. Upon pathway disruption, stem cells become overactivated, hindering terminal differentiation and weakening barrier function. Upstream, LC activity is tuned by the local microbial environment in a rheostat-like fashion, coupling commensal sensing to stem cell dynamics. Our findings provide a general framework for how barrier tissues achieve adaptive homeostasis amid continual external fluctuations.
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