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Publication : Endogenous retroviruses promote homeostatic and inflammatory responses to the microbiota.

First Author  Lima-Junior DS Year  2021
Journal  Cell Volume  184
Issue  14 Pages  3794-3811.e19
PubMed ID  34166614 Mgi Jnum  J:314360
Mgi Id  MGI:6728429 Doi  10.1016/j.cell.2021.05.020
Citation  Lima-Junior DS, et al. (2021) Endogenous retroviruses promote homeostatic and inflammatory responses to the microbiota. Cell 184(14):3794-3811.e19
abstractText  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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