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

Published in: Nature Immunology, 2018, 19 (8), pp.809+. ⟨10.1038/s41590-018-0144-9⟩

Authors: Wilson Castro, Sonia T. Chelbi, Charlene Niogret, Cristina Ramon-Barros, Suzanne P. M. Welten, Kevin Osterheld, Haiping Wang, Giorgia Rota, Leonor Morgado, Eric Vivier, Miro E. Raeber, Onur Boyman, Mauro Delorenzi, David Barras, Ping-Chih Ho, Annette Oxenius, Greta Guarda

Summary

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.

Link to HAL – hal-04831554

Link to DOI – 10.1038/s41590-018-0144-9