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

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 acc...

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Vydáno v:	The Journal of clinical investigation Ročník 130; číslo 9; s. 4587 - 4600
Hlavní autoři:	Matthias, Julia, Heink, Sylvia, Picard, Felix, Zeiträg, Julia, Kolz, Anna, Chao, Ying-Yin, Soll, Dominik, de Almeida, Gustavo P., Glasmacher, Elke, Jacobsen, Ilse D., Riedel, Thomas, Peters, Anneli, Floess, Stefan, Huehn, Jochen, Baumjohann, Dirk, Huber, Magdalena, Korn, Thomas, Zielinski, Christina E.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States American Society for Clinical Investigation 01.09.2020
Témata:	Animals Anti-inflammatory agents Autoimmunity Biomedical research Bone morphogenetic proteins Cell fate Cellular Microenvironment - drug effects Cellular Microenvironment - immunology Cloning Cytokines Cytokines - genetics Cytokines - immunology Dietary intake Experimental allergic encephalomyelitis Foxp3 protein Genotype & phenotype Helper cells Humans Immunological tolerance Inflammation - genetics Inflammation - immunology Inflammation - pathology Inflammatory diseases Lymphocytes Lymphocytes T MAP kinase MAP Kinase Signaling System - drug effects MAP Kinase Signaling System - genetics MAP Kinase Signaling System - immunology Mice Mice, Transgenic Microenvironments Pathogenicity Pathogens Scientific equipment industry Sodium chloride Sodium Chloride, Dietary - pharmacology Software industry Specialization T cell receptors T cells Th17 Cells - immunology Th17 Cells - pathology Transforming growth factors United States Germany Adaptive immunity Inflammation Immunology T cells
ISSN:	0021-9738, 1558-8238, 1558-8238
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3 Authorship note: SH and FP contributed equally to this work. MH and TK contributed equally to this work.
ISSN:	0021-9738 1558-8238 1558-8238
DOI:	10.1172/JCI137786