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


Castro, Wilson; Chelbi, Sonia T; Niogret, Charlène; Ramon-Barros, Cristina; Welten, Suzanne P M; Osterheld, Kevin; Wang, Haiping; Rota, Giorgia; Morgado, Leonor; Vivier, Eric; Raeber, Miro E; Boyman, Onur; Delorenzi, Mauro; Barras, David; Ho, Ping-Chih; Oxenius, Annette; Guarda, Greta (2018). The transcription factor Rfx7 limits metabolism of NK cells and promotes their maintenance and immunity. Nature Immunology, 19(8):809-820.

Abstract

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.

Abstract

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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Immunology
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Immunology
Language:English
Date:1 August 2018
Deposited On:08 Mar 2019 08:36
Last Modified:08 Mar 2019 08:36
Publisher:Nature Publishing Group
ISSN:1529-2908
OA Status:Closed
Publisher DOI:https://doi.org/10.1038/s41590-018-0144-9
PubMed ID:29967452

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