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PMID: 29967452 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Nature immunology ·Vol. 19 ·No. 8 ·2018-00-00 ·Pages 809-820

Castro W, Chelbi ST, Niogret C, Ramon-Barros C, Welten SPM, Osterheld K, Wang H, Rota G, Morgado L, Vivier E, Raeber ME, Boyman O, Delorenzi M, Barras D, Ho PC, Oxenius A, Guarda G

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.

MeSH Terms
Animals Cell Proliferation Cell Survival Cells, Cultured Chimera Energy Metabolism Gene Regulatory Networks Immunity, Cellular/genetics Immunity, Innate/genetics Interleukin-15/metabolism Janus Kinases/metabolism Killer Cells, Natural/immunology,metabolism Mice Mice, Inbred C57BL Mice, Knockout Regulatory Factor X1/genetics,metabolism Signal Transduction TOR Serine-Threonine Kinases/genetics,metabolism
Chemicals
Interleukin-15 Regulatory Factor X1 Janus Kinases TOR Serine-Threonine Kinases
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Castro Wilson
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Chelbi Sonia T ORCID
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland. | Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland.
Niogret Charlène
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Ramon-Barros Cristina
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Welten Suzanne P M
Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
Osterheld Kevin
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Wang Haiping
Ludwig Center for Cancer Research of the University of Lausanne, Epalinges, Switzerland. | Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland.
Rota Giorgia
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Morgado Leonor
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Vivier Eric ORCID
Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, Inserm, CNRS, Marseille, France. | Service d'Immunologie, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France. | Innate Pharma Research Labs., Innate Pharma, Marseille, France.
Raeber Miro E ORCID
Department of Immunology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Boyman Onur
Department of Immunology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Delorenzi Mauro ORCID
Ludwig Center for Cancer Research of the University of Lausanne, Epalinges, Switzerland. | Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland. | Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
Barras David
Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
Ho Ping-Chih ORCID
Ludwig Center for Cancer Research of the University of Lausanne, Epalinges, Switzerland. | Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland.
Oxenius Annette
Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
Guarda Greta ORCID
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland. greta.guarda@irb.usi.ch. | Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland. greta.guarda@irb.usi.ch.
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/s41590-018-0144-9
Email
greta.guarda@irb.usi.ch
Published
2018-00-00
Epub
2018-00-02
Pages
809-820
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC6428260
Subset
IM
Corrections
CommentIn
PMID: 29980740
External Links
PubMed source DOI: 10.1038/s41590-018-0144-9 PMC Full Text View journal details
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