دورية أكاديمية
Sodium perturbs mitochondrial respiration and induces dysfunctional Tregs.
| العنوان: | Sodium perturbs mitochondrial respiration and induces dysfunctional Tregs. |
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| المؤلفون: | Côrte-Real, Beatriz F, Hamad, Ibrahim, Arroyo Hornero, Rebeca, Geisberger, Sabrina, Roels, Joris, Van Zeebroeck, Lauren, Dyczko, Aleksandra, van Gisbergen, Marike W, KURNIAWAN, Henry, Wagner, Allon, Yosef, Nir, Weiss, Susanne N Y, Schmetterer, Klaus G, Schröder, Agnes, Krampert, Luka, Haase, Stefanie, Bartolomaeus, Hendrik, Hellings, Niels, Saeys, Yvan, Dubois, Ludwig J, BRENNER, Dirk, Kempa, Stefan, Hafler, David A, Stegbauer, Johannes, Linker, Ralf A, Jantsch, Jonathan, Müller, Dominik N, Kleinewietfeld, Markus |
| المصدر: | Cell Metabolism, 35 (2), 299 - 315.e8 (2023-02-07) |
| بيانات النشر: | Cell Press |
| سنة النشر: | 2023 |
| المجموعة: | University of Luxembourg: ORBilu - Open Repository and Bibliography |
| مصطلحات موضوعية: | FOXP3, autoimmunity, high salt, mitochondrial respiration, regulatory T cells, Sodium, Forkhead Transcription Factors, Humans, Forkhead Transcription Factors/metabolism, Sodium/metabolism, T-Lymphocytes, Regulatory, Physiology, Molecular Biology, Cell Biology, Human health sciences, Immunology & infectious disease, Sciences de la santé humaine, Immunologie & maladie infectieuse |
| الوصف: | peer reviewed ; 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 mitochondrial metabolism, but contributing factors remain elusive. High salt (HS) has been identified to alter immune 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1550-4131 1932-7420 |
| العلاقة: | https://api.elsevier.com/content/article/PII:S1550413123000098?httpAccept=text/xmlTest; urn:issn:1550-4131; urn:issn:1932-7420; https://orbilu.uni.lu/handle/10993/58744Test; info:hdl:10993/58744; https://orbilu.uni.lu/bitstream/10993/58744/1/C%c3%b4rte-Real%20BF%20et%20al%202023%20Cell%20Metabolism%2035%20299-315_1-s2.0-S1550413123000098-main.pdfTest; scopus-id:2-s2.0-85147586424; info:pmid:36754020; wos:001041611700001 |
| DOI: | 10.1016/j.cmet.2023.01.009 |
| الإتاحة: | https://doi.org/10.1016/j.cmet.2023.01.009Test https://orbilu.uni.lu/handle/10993/58744Test https://orbilu.uni.lu/bitstream/10993/58744/1/C%c3%b4rte-Real%20BF%20et%20al%202023%20Cell%20Metabolism%2035%20299-315_1-s2.0-S1550413123000098-main.pdfTest |
| حقوق: | open access ; http://purl.org/coar/access_right/c_abf2Test ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.3A59D652 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15504131 19327420 |
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| DOI: | 10.1016/j.cmet.2023.01.009 |