Corte-Real, Beatriz F. and Hamad, Ibrahim and Hornero, Rebeca Arroyo and Geisberger, Sabrina and Roels, Joris and Van Zeebroeck, Lauren and Dyczko, Aleksandra and van Gisbergen, Marike W. and Kurniawan, Henry and Wagner, Allon and Yoset, Nir and Weiss, Susanne N. Y. and Schmetterer, Klaus G. and Schroeder, Agnes and Krampert, Luka and Haase, Stefanie and Bartolomaeus, Hendrik and Hellings, Niels and Saeys, Yvan and Dubois, Ludwig J. and Brenner, Dirk and Kempa, Stefan and Hafler, David A. and Stegbauer, Johannes and Linker, Ralf A. and Jantsch, Jonathan and Mueller, Dominik N. and Kleinewietfeld, Markus (2023) Sodium perturbs mitochondrial respiration and induces dysfunctional Tregs. CELL METABOLISM, 35 (2). 299-+. ISSN 1550-4131, 1932-7420
Full text not available from this repository. (Request a copy)Abstract
FOXP3+ regulatory T cells (Tregs) are central for peripheral tolerance, and their deregulation is associated with autoimmunity. Dysfunctional autoimmune Tregs display pro-inflammatory features and altered mito-chondrial metabolism, but contributing factors remain elusive. High salt (HS) has been identified to alter im-mune function and to promote autoimmunity. By investigating longitudinal transcriptional changes of human Tregs, we identified that HS induces metabolic reprogramming, recapitulating features of autoimmune Tregs. Mechanistically, extracellular HS raises intracellular Na+, perturbing mitochondrial respiration by interfering with the electron transport chain (ETC). Metabolic disturbance by a temporary HS encounter or complex III blockade rapidly induces a pro-inflammatory signature and FOXP3 downregulation, leading to long-term dysfunction in vitro and in vivo. The HS-induced effect could be reversed by inhibition of mitochondrial Na+/Ca2+ exchanger (NCLX). Our results indicate that salt could contribute to metabolic reprogramming and that short-term HS encounter perturb metabolic fitness and long-term function of human Tregs with important implications for autoimmunity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REGULATORY T-CELLS; AUTOIMMUNE-DISEASE; NA+/CA2+ EXCHANGE; TH17 CELLS; CHLORIDE; ATHEROSCLEROSIS; HOMEOSTASIS; INHIBITION; PLASTICITY; INDUCTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Lehrstuhl für Neurologie Medicine > Lehrstuhl für Zahnärztliche Prothetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Jan 2024 09:57 |
| Last Modified: | 30 Jan 2024 09:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60493 |
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