Salt generates antiinflammatory Th17 cells but amplifies pathogenicity in proinflammatory cytokine microenvironments.

Autor:	Matthias J; Institute of Virology, Technical University of Munich, Munich, Germany.; German Center for Infection Research, Partner Site Munich, Munich, Germany.; Department of Cellular Immunoregulation, Charité - Universitätsmedizin Berlin, Berlin, Germany., Heink S; Klinikum rechts der Isar, Department of Experimental Neuroimmunology, Technical University of Munich, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Picard F; Institute for Medical Microbiology and Hygiene, University of Marburg, Marburg, Germany., Zeiträg J; Institute for Immunology, Biomedical Center, Faculty of Medicine, Ludwig Maximilian University of Munich (LMU Munich), Planegg-Martinsried, Germany., Kolz A; Institute of Clinical Neuroimmunology, Hospital and Biomedical Center of LMU Munich, Planegg-Martinsried, Germany., Chao YY; Institute of Virology, Technical University of Munich, Munich, Germany.; German Center for Infection Research, Partner Site Munich, Munich, Germany.; TranslaTUM, Technical University of Munich, Munich, Germany., Soll D; Institute of Virology, Technical University of Munich, Munich, Germany.; German Center for Infection Research, Partner Site Munich, Munich, Germany., de Almeida GP; Institute of Virology, Technical University of Munich, Munich, Germany.; German Center for Infection Research, Partner Site Munich, Munich, Germany.; TranslaTUM, Technical University of Munich, Munich, Germany., Glasmacher E; Roche Innovation Center Munich, pRED, Large Molecule Research, Penzberg, Germany., Jacobsen ID; Research Group Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.; Institute of Microbiology, Friedrich Schiller University, Jena, Germany., Riedel T; Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig and German Center for Infection Research, Partner Site Hannover-Braunschweig, Hannover-Braunschweig, Germany., Peters A; Institute of Clinical Neuroimmunology, Hospital and Biomedical Center of LMU Munich, Planegg-Martinsried, Germany., Floess S; Department of Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany., Huehn J; Department of Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany., Baumjohann D; Institute for Immunology, Biomedical Center, Faculty of Medicine, Ludwig Maximilian University of Munich (LMU Munich), Planegg-Martinsried, Germany., Huber M; Institute for Medical Microbiology and Hygiene, University of Marburg, Marburg, Germany., Korn T; Klinikum rechts der Isar, Department of Experimental Neuroimmunology, Technical University of Munich, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Zielinski CE; Institute of Virology, Technical University of Munich, Munich, Germany.; German Center for Infection Research, Partner Site Munich, Munich, Germany.; Department of Cellular Immunoregulation, Charité - Universitätsmedizin Berlin, Berlin, Germany.; TranslaTUM, Technical University of Munich, Munich, Germany.
Jazyk:	angličtina
Zdroj:	The Journal of clinical investigation [J Clin Invest] 2020 Sep 01; Vol. 130 (9), pp. 4587-4600.
DOI:	10.1172/JCI137786
Abstrakt:	Th cells integrate signals from their microenvironment to acquire distinct specialization programs for efficient clearance of diverse pathogens or for immunotolerance. Ionic signals have recently been demonstrated to affect T cell polarization and function. Sodium chloride (NaCl) was proposed to accumulate in peripheral tissues upon dietary intake and to promote autoimmunity via the Th17 cell axis. Here, we demonstrate that high-NaCl conditions induced a stable, pathogen-specific, antiinflammatory Th17 cell fate in human T cells in vitro. The p38/MAPK pathway, involving NFAT5 and SGK1, regulated FoxP3 and IL-17A expression in high-NaCl conditions. The NaCl-induced acquisition of an antiinflammatory Th17 cell fate was confirmed in vivo in an experimental autoimmune encephalomyelitis (EAE) mouse model, which demonstrated strongly reduced disease symptoms upon transfer of T cells polarized in high-NaCl conditions. However, NaCl was coopted to promote murine and human Th17 cell pathogenicity, if T cell stimulation occurred in a proinflammatory and TGF-β-low cytokine microenvironment. Taken together, our findings reveal a context-dependent, dichotomous role for NaCl in shaping Th17 cell pathogenicity. NaCl might therefore prove beneficial for the treatment of chronic inflammatory diseases in combination with cytokine-blocking drugs.
Databáze:	MEDLINE
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