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The transcription factor Rfx7 limits metabolism of NK cells promoting their maintenance and immunity

ABSTRACT: The transcription factor Rfx7 limits metabolism of NK cells promoting their maintenance and immunity

PROVIDER: PRJNA450613 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7015650.fastq.gz	Fastqsanger.gz
	SRR7015651.fastq.gz	Fastqsanger.gz
	SRR7015652.fastq.gz	Fastqsanger.gz
	SRR7015653.fastq.gz	Fastqsanger.gz
	SRR7015654.fastq.gz	Fastqsanger.gz

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The transcription factor Rfx7 limits metabolism of NK cells promoting their maintenance and immunity

Project description:Regulatory factor X 7 (Rfx7) is an uncharacterized member of a family of transcription factors playing essential functions in ciliogenesis and immunity. Given the prominent expression of Rfx7 in lymphoid organs, we generated mice with Rfx7-deletion in the hematopoietic compartment. We assessed the function of Rfx7 in natural killer cells, which are innate lymphoid cells that protect from viral infections and cancer. By comparing the transcriptome of Rfx7-deficient and control NK cells isolated from bone marrow and spleen, we identified negative regulators of cell metabolism among the genes regulated by this transcription factor.

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Project description:Regulatory factor X 7 (Rfx7) is an uncharacterized transcription factor belonging to a family involved in ciliogenesis and immunity. Here, we found that deletion of Rfx7 leads to a decrease in natural killer (NK) cell maintenance and immunity in vivo. Genomic approaches showed that Rfx7 coordinated a transcriptional network controlling cell metabolism. Rfx7-/- NK lymphocytes presented increased size, granularity, proliferation, and energetic state, whereas genetic reduction of mTOR activity mitigated those defects. Notably, Rfx7-deficient NK lymphocytes were rescued by interleukin 15 through engagement of the Janus kinase (Jak) pathway, thus revealing the importance of this signaling for maintenance of such spontaneously activated NK cells. Rfx7 therefore emerges as a novel transcriptional regulator of NK cell homeostasis and metabolic quiescence.

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