Commensal microbiota regulates skin barrier function and repair via signaling through the aryl hydrocarbon receptor

被引:183
作者
Uberoi, Aayushi [1 ]
Bartow-McKenney, Casey [1 ]
Zheng, Qi [1 ]
Flowers, Laurice [1 ]
Campbell, Amy [1 ]
Knight, Simon A. B. [1 ]
Chan, Neal [1 ]
Wei, Monica [1 ]
Lovins, Victoria [1 ]
Bugayev, Julia [1 ]
Horwinski, Joseph [1 ]
Bradley, Charles [2 ]
Meyer, Jason [3 ,4 ]
Crumrine, Debra [3 ,4 ]
Sutter, Carrie Hayes [5 ]
Elias, Peter [3 ,4 ]
Mauldin, Elizabeth [2 ]
Sutter, Thomas R. [5 ]
Grice, Elizabeth A. [1 ]
机构
[1] Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA
[3] San Francisco VA Med Ctr, Dermatol Serv, San Francisco, CA USA
[4] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA USA
[5] Univ Memphis, W Harry Feinstone Ctr Genom Res, Dept Biol Sci, Memphis, TN 38152 USA
关键词
WATER-LOSS; MICE; AHR; DIFFERENTIATION; KERATINOCYTES; TRANSCRIPTION; DERMATITIS; EXPRESSION; CELLS; LIVER;
D O I
10.1016/j.chom.2021.05.011
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The epidermis forms a barrier that defends the body from desiccation and entry of harmful substances, while also sensing and integrating environmental signals. The tightly orchestrated cellular changes needed for the formation and maintenance of this epidermal barrier occur in the context of the skin microbiome. Using germfree mice, we demonstrate the microbiota is necessary for proper differentiation and repair of the epidermal barrier, These effects are mediated by microbiota signaling through the aryl hydrocarbon receptor (AHR) in keratinocytes, a xenobiotic receptor also implicated in epidermal differentiation. Mice lacking keratinocyte AHR are more susceptible to barrier damage and infection, during steady-state and epicutaneous sensitization. Colonization with a defined consortium of human skin isolates restored barrier competence in an AHR-dependent manner. We reveal a fundamental mechanism whereby the microbiota regulates skin barrier formation and repair, which has far-reaching implications for the numerous skin disorders characterized by epidermal barrier dysfunction.
引用
收藏
页码:1235 / +
页数:22
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