生物
炎症
免疫
内生
内源性逆转录病毒
免疫系统
细胞生物学
转录因子
干扰素
免疫学
先天免疫系统
平衡
遗传学
基因
内分泌学
基因组
作者
Djalma S. Lima-Júnior,Siddharth R. Krishnamurthy,Nicolas Bouladoux,Nicholas Collins,Seong-Ji Han,Erin Chen,Michael G. Constantinides,Verena M. Link,Ai Ing Lim,Michel Enamorado,Christophe Cataisson,Louis Gil,Indira Rao,Taylor K. Farley,Galina Koroleva,Jan Attig,Stuart H. Yuspa,Michael A. Fischbach,George Kassiotis,Yasmine Belkaid
出处
期刊:Cell
[Elsevier]
日期:2021-07-01
卷期号:184 (14): 3794-3811.e19
被引量:91
标识
DOI:10.1016/j.cell.2021.05.020
摘要
The microbiota plays a fundamental role in regulating host immunity. However, the processes involved in the initiation and regulation of immunity to the microbiota remain largely unknown. Here, we show that the skin microbiota promotes the discrete expression of defined endogenous retroviruses (ERVs). Keratinocyte-intrinsic responses to ERVs depended on cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes protein (STING) signaling and promoted the induction of commensal-specific T cells. Inhibition of ERV reverse transcription significantly impacted these responses, resulting in impaired immunity to the microbiota and its associated tissue repair function. Conversely, a lipid-enriched diet primed the skin for heightened ERV- expression in response to commensal colonization, leading to increased immune responses and tissue inflammation. Together, our results support the idea that the host may have co-opted its endogenous virome as a means to communicate with the exogenous microbiota, resulting in a multi-kingdom dialog that controls both tissue homeostasis and inflammation.
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