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Endogenous retrovirus control of homeostatic and inflammatory responses to the microbiota [RNA-seq 2]

ABSTRACT: Endogenous retrovirus control of homeostatic and inflammatory responses to the microbiota [RNA-seq 2]

PROVIDER: PRJNA720749 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14193600_1.fastq.gz	Fastqsanger.gz
	SRR14193600_2.fastq.gz	Fastqsanger.gz
	SRR14193601_1.fastq.gz	Fastqsanger.gz
	SRR14193601_2.fastq.gz	Fastqsanger.gz
	SRR14193602_1.fastq.gz	Fastqsanger.gz

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Endogenous retrovirus control of homeostatic and inflammatory responses to the microbiota

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Endogenous retrovirus control of homeostatic and inflammatory responses to the microbiota [scRNA-seq]

Project description:How the homeostatic dialogue between the host and its microbiota is initiated remains largely unknown. Here, we show that immune response to the skin microbiota is dependent on activity of endogenous retroviruses. Notably, response to the microbiota promotes a discrete transcriptional induction of retroelements. As such, keratinocyte intrinsic sensing of endogenous retrovirus (ERV) derived DNA via cGAS/STING promotes the induction of commensal specific T cells including CD8+, CD4+ and MAIT cells. Consequently, inhibition of reverse transcriptase activity impairs both homeostatic immunity to the microbiota and associated tissue repair function. On the other hand, altered diet and in particular increase in dietary lipids primed the skin for aberrant ERV expression in the context of microbiota exposure leading to tissue inflammation. Together our results support the idea that the host may have coopted its endogenous virome as a means to communicate with exogenous microbiota resulting in a multikingdom dialogue that controls both tissue homeostasis and inflammation.

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Endogenous retrovirus control of homeostatic and inflammatory responses to the microbiota

Project description:This SuperSeries is composed of the SubSeries listed below.

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Endogenous retroviruses promote homeostatic and inflammatory responses to the microbiota.

Project description: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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