Journal
CELL REPORTS
Volume 30, Issue 5, Pages 1515-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.01.002
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Funding
- Canadian Institutes of Health Research (CIHR) [PJT-148821]
- Canada Research Chair program
- Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN/05541-2017]
- Intramural Research Program of NIAID, NIH
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI000959] Funding Source: NIH RePORTER
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Regulatory T (Treg) cells integrate diverse environmental signals to modulate their function for optimal suppression. Translational regulation represents a favorable mechanism for Treg cell environmental sensing and adaptation. In this study, we carry out an unbiased screen of the Treg cell translatome and identify serum/glucocorticoid-regulated kinase 1 (SGK1), a known salt sensor in T cells, as being preferentially translated in activated Treg cells. We show that high salt (HS) drives thymic Treg cells to adopt a T helper type 17 (Th17)-like phenotype and enhances generation of Th17-like induced Treg cells in a SGK1 -dependent manner, all the while maintaining suppressive function. Salt-mediated Th17-like differentiation of Treg cells was evident in mice fed with HS diet or injected with HS-preconditioned T cells. Overall, SGK1 enables Treg cells to adapt their function in response to environmental cues. By understanding these environmental-sensing mechanisms, we envision targeted approaches to fine-tune Treg cell function for better control of inflammation.
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