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Environmental modulators of the immune cell balance in health and disease

Total Cost €


EC-Contrib. €






Project "ENVIROIMMUNE" data sheet

The following table provides information about the project.


Organization address
postcode: 9052

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Belgium [BE]
 Total cost 1˙499˙041 €
 EC max contribution 1˙499˙041 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-08-01   to  2020-07-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    VIB BE (ZWIJNAARDE - GENT) coordinator 1˙499˙041.00


 Project objective

The incidence of autoimmune diseases in developed societies is increasing at high rates, but the underlying cause for this phenomenon has not been elucidated yet. Since the genetic architect remains considerably stable, this increase is likely associated with changes in the environment. Autoimmunity is linked to an imbalance of pro-inflammatory Th17 cells and anti-inflammatory Foxp3 regulatory T cells (Treg). However, little is known regarding environmental factors that influence the Th17/Treg balance. We recently discovered that a sodium-rich diet severely exacerbates experimental autoimmune encephalomyelitis (EAE) through an increased induction of pathogenic Th17 cells. Surprisingly, our preliminary data indicate that high-salt conditions also significantly impair Treg function, resembling a phenotype observed in several human autoimmune diseases. In addition, we have evidence that a high-salt diet affects the gut microbiota, implicating possible indirect effects on immune cells in vivo. Based on these findings we hypothesize that excess dietary salt represents an environmental risk factor for autoimmune diseases by modulating the Th17/Treg balance by several direct and indirect mechanisms. To address this hypothesis we will 1) examine the underlying mechanisms of high-salt induced Treg dysfunction and effects on the Treg/Th17 balance by molecular and functional analysis in vitro and compare it to known risk variants of human autoimmune diseases, and 2) define direct and indirect effects of excess dietary salt on the Th17/Treg balance and autoimmunity in vivo and explore potential novel pathways for targeted interventions. Thus, the proposed study will uncover the impact of a newly discovered environmental modulator of the immune cell balance and will ultimately pave the way for new approaches in therapy and prevention of autoimmune diseases.


year authors and title journal last update
List of publications.
2017 Katrina J. Binger, Beatriz F. Côrte-Real, Markus Kleinewietfeld
Immunometabolic Regulation of Interleukin-17-Producing T Helper Cells: Uncoupling New Targets for Autoimmunity
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2017.00311
Frontiers in Immunology 8 2019-05-29
2017 Nicola Wilck, Mariana G. Matus, Sean M. Kearney, Scott W. Olesen, Kristoffer Forslund, Hendrik Bartolomaeus, Stefanie Haase, Anja Mähler, András Balogh, Lajos Markó, Olga Vvedenskaya, Friedrich H. Kleiner, Dmitry Tsvetkov, Lars Klug, Paul I. Costea, Shinichi Sunagawa, Lisa Maier, Natalia Rakova, Valentin Schatz, Patrick Neubert, Christian Frätzer, Alexander Krannich, Maik Gollasch, Diana A. Grohme, Beatriz F. Côrte-Real, Roman G. Gerlach, Marijana Basic, Athanasios Typas, Chuan Wu, Jens M. Titze, Jonathan Jantsch, Michael Boschmann, Ralf Dechend, Markus Kleinewietfeld, Stefan Kempa, Peer Bork, Ralf A. Linker, Eric J. Alm, Dominik N. Müller
Salt-responsive gut commensal modulates TH17 axis and disease
published pages: , ISSN: 0028-0836, DOI: 10.1038/nature24628
Nature 2019-05-29
2018 Olga Matveeva, Jeroen F.J. Bogie, Jerome J.A. Hendriks, Ralf A. Linker, Aiden Haghikia, Markus Kleinewietfeld
Western lifestyle and immunopathology of multiple sclerosis
published pages: , ISSN: 0077-8923, DOI: 10.1111/nyas.13583
Annals of the New York Academy of Sciences 2019-05-29
2017 Anna Hammer, Anne Schliep, Stefanie Jörg, Aiden Haghikia, Ralf Gold, Markus Kleinewietfeld, Dominik N. Müller, Ralf A. Linker
Impact of combined sodium chloride and saturated long-chain fatty acid challenge on the differentiation of T helper cells in neuroinflammation
published pages: , ISSN: 1742-2094, DOI: 10.1186/s12974-017-0954-y
Journal of Neuroinflammation 14/1 2019-05-29
2016 Stefanie Jörg, Diana A. Grohme, Melanie Erzler, Marilene Binsfeld, Aiden Haghikia, Dominik N. Müller, Ralf A. Linker, Markus Kleinewietfeld
Environmental factors in autoimmune diseases and their role in multiple sclerosis
published pages: 4611-4622, ISSN: 1420-682X, DOI: 10.1007/s00018-016-2311-1
Cellular and Molecular Life Sciences 73/24 2019-05-29
2018 Ralf Willebrand, Markus Kleinewietfeld
The role of salt for immune cell function and disease
published pages: , ISSN: 0019-2805, DOI: 10.1111/imm.12915
Immunology 2019-05-29
2016 Stefanie Jörg, Jan Kissel, Arndt Manzel, Markus Kleinewietfeld, Aiden Haghikia, Ralf Gold, Dominik N. Müller, Ralf A. Linker
High salt drives Th17 responses in experimental autoimmune encephalomyelitis without impacting myeloid dendritic cells
published pages: 212-222, ISSN: 0014-4886, DOI: 10.1016/j.expneurol.2016.03.010
Experimental Neurology 279 2019-05-27
2016 A. S. Arterbery, A. Osafo-Addo, Y. Avitzur, M. Ciarleglio, Y. Deng, S. J. Lobritto, M. Martinez, D. A. Hafler, M. Kleinewietfeld, U. D. Ekong
Production of Proinflammatory Cytokines by Monocytes in Liver-Transplanted Recipients with De Novo Autoimmune Hepatitis Is Enhanced and Induces TH1-like Regulatory T Cells
published pages: 4040-4051, ISSN: 0022-1767, DOI: 10.4049/jimmunol.1502276
The Journal of Immunology 196/10 2019-05-27

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