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Salt generates antiinflammatory Th17 cells but amplifies pathogenicity in proinflammatory cytokine microenvironments
by
Matthias, Julia
, Jacobsen, Ilse D.
, Picard, Felix
, Floess, Stefan
, Peters, Anneli
, Korn, Thomas
, Huehn, Jochen
, Glasmacher, Elke
, Baumjohann, Dirk
, de Almeida, Gustavo P.
, Huber, Magdalena
, Kolz, Anna
, Zielinski, Christina E.
, Zeiträg, Julia
, Riedel, Thomas
, Heink, Sylvia
, Chao, Ying-Yin
, Soll, Dominik
in
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
2020
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Salt generates antiinflammatory Th17 cells but amplifies pathogenicity in proinflammatory cytokine microenvironments
by
Matthias, Julia
, Jacobsen, Ilse D.
, Picard, Felix
, Floess, Stefan
, Peters, Anneli
, Korn, Thomas
, Huehn, Jochen
, Glasmacher, Elke
, Baumjohann, Dirk
, de Almeida, Gustavo P.
, Huber, Magdalena
, Kolz, Anna
, Zielinski, Christina E.
, Zeiträg, Julia
, Riedel, Thomas
, Heink, Sylvia
, Chao, Ying-Yin
, Soll, Dominik
in
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
2020
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Salt generates antiinflammatory Th17 cells but amplifies pathogenicity in proinflammatory cytokine microenvironments
by
Matthias, Julia
, Jacobsen, Ilse D.
, Picard, Felix
, Floess, Stefan
, Peters, Anneli
, Korn, Thomas
, Huehn, Jochen
, Glasmacher, Elke
, Baumjohann, Dirk
, de Almeida, Gustavo P.
, Huber, Magdalena
, Kolz, Anna
, Zielinski, Christina E.
, Zeiträg, Julia
, Riedel, Thomas
, Heink, Sylvia
, Chao, Ying-Yin
, Soll, Dominik
in
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
2020
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Salt generates antiinflammatory Th17 cells but amplifies pathogenicity in proinflammatory cytokine microenvironments
Journal Article
Salt generates antiinflammatory Th17 cells but amplifies pathogenicity in proinflammatory cytokine microenvironments
2020
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Overview
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.
Publisher
American Society for Clinical Investigation
Subject
/ Cellular Microenvironment - drug effects
/ Cellular Microenvironment - immunology
/ Cloning
/ Experimental allergic encephalomyelitis
/ Humans
/ MAP Kinase Signaling System - drug effects
/ MAP Kinase Signaling System - genetics
/ MAP Kinase Signaling System - immunology
/ Mice
/ Scientific equipment industry
/ Sodium Chloride, Dietary - pharmacology
/ T cells
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