Article
High dietary salt aggravates autoimmune neuroinflammation via induction of Th17 cells
Search Medline for
Authors
-
Arndt Manzel
- University of Erlangen, Erlangen, Germany; International Graduate School for Neuroscience, Ruhr-University, Bochum, Germany
-
Jens Titze
- University of Erlangen, Erlangen, Germany; Vanderbilt University, Nashville, TN, Germany
-
Dominik N. Muller
- University of Erlangen, Erlangen, Germany; Max-Delbrueck-Center, Berlin, Germany
-
Ralf A. Linker
- University of Erlangen, Erlangen, Germany
| Published: | September 11, 2012 |
|---|
Outline
Text
Over the past half century there has been a marked increase in the incidence of multiple sclerosis (MS), a neuroinflammatory disease that may partly be driven by the novel Th17 subset of helper T cells. This rapid epidemiological development must be related to changes in the environment. Excess salt (sodium chloride, NaCl) uptake increased along with consumption of “western diet” and processed foods predominantly in developed countries, where MS incidence is high.
To explore if salt-load may influence autoimmune neuroinflammation, we investigated effects of a high salt diet (HSD) in murine myelin oligodendrocyte glycoprotein (MOG) induced experimental autoimmune encephalomyelitis (EAE) which mimics aspects of human MS.
Salt-load led to a significant exacerbation of MOG-EAE. While mice on a HSD (4%NaCl) suffered from moderate paraparesis mice on a normal diet (0.4% NaCl) only developed gait ataxia (n=12 p.g., p<0.05). This finding was corroborated by histological analyses. Spinal cord lesions from mice in the HSD group showed greater infiltration of Mac3+ macrophages/microglia (n=5 p.g. p<0.05) and CD3+ T cells (n=6–7 p.g., p<0.05). Analysis of gene expression under HSD revealed a shift towards Th17 driven autoimmunity. Expression of IL-17A, the prototypic Th17 effector cytokine, but not interferon-gamma was elevated in the spleen (n=5–6 p.g. p<0.05) and spinal cord (n=5–6 p.g. p<0.05) of mice on a HSD.In vitrorestimulation of MOG primed splenocytes in medium with a surplus of 40 mM NaCl increased IL-17A but not interferon-gamma secretion into the culture supernatant. Flow cytometric analysis of the same MOG restimulated splenocytes showed increased frequencies of CD4+IL17A+ cells (n=4–5 p<0.01). To dissect the NaCl effect on a cellular level, we performedin vitroT cell polarization assays. Increasing medium NaCl concentration by 40 mM boosts Th17 cell polarization of naïve T cells either stimulated by CD3 antibody or antigen presenting cells up to 5-fold (n=3 p.g. p<0.001).
Our findings demonstrate that a high salt diet exacerbates MOG-EAE by boosting Th17 cells and suggest that excess sodium uptake may be considered as a new dietary factor possibly influencing complex autoimmune diseases such as MS.
