2026年10月29日，美国洛克菲勒大学Anita Gola等科学家在《科学》（Science）发表研究，揭示了共生菌调控的免疫变阻器如何精细调节皮肤屏障适应性。

在皮肤表面，表皮必须在干细胞更新与屏障维持之间取得平衡，以承受环境应激并抵御病原体。在本研究中，研究人员在小鼠中鉴定出一种微生物-免疫-上皮反馈机制，该机制将环境信息整合到干细胞调控中。具体而言，研究人员表明，朗格汉斯细胞（LCs）——一种上皮内巨噬细胞群体——通过产生前列腺素E2来协调这一回路，前列腺素E2在稳态下抑制干细胞增殖、促进表皮分化并维持屏障完整性。当该通路被破坏时，干细胞过度激活，阻碍终末分化并削弱屏障功能。在上游，LC活性由局部微生物环境以变阻器样方式调节，将共生菌感知与干细胞动态耦合。研究人员的发现为屏障组织如何在持续的外部波动中实现适应性稳态提供了一个通用框架。

附：英文原文

Title: A commensally regulated immune rheostat fine-tunes skin barrier fitness

Author: Anita Gola, Rohith Srinivas, Elias G. Rodig, Marina Schernthanner, Merve Deniz Abdusselamoglu, Matthew T. Tierney, Natalie J. Alexander, Kevin A. U. Gonzales, Sairaj M. Sajjath, Luis F. Soto-Ugaldi, Alain R. Bonny, Elaine Fuchs

Issue&Volume: 2026-10-29

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.

DOI: 10.1126/science.aee5920

Source:https://www.science.org/doi/10.1126/science.aee5920