A commensally regulated immune rheostat fine-tunes skin barrier fitness

We identify Langerhans cells (LCs) as key regulators of this balance through a prostaglandin E₂ (PGE₂)–dependent feedback circuit. By producing PGE₂, LCs restrain epidermal stem cell (EpSC) proliferation and promote differentiation, maintaining barrier integrity under homeostatic conditions.

Disruption of this pathway leads to excessive EpSC activation, impaired differentiation, and compromised barrier function. LC activity is tuned by the local microbial environment in a rheostat-like fashion, coupling commensal sensing to EpSC control. These findings reveal an immune–epithelial feedback mechanism that integrates environmental information into stem cell regulation, providing a general framework for how barrier tissues achieve adaptive homeostasis amid continual external challenge.