Abstract Details

Title High Dietary Salt Aggravates Experimental Neuroinflammation in Mice Via Induction of Th17 Cells

Topic MS and Related Diseases

Presentation(s) S50 - (-)

Poster/Presentation
Number 003

Objective

Background Over the past half-century, there has been a marked increase in the incidence of MS that may be driven by changes in the environment. Excess salt (NaCl) uptake could be a contributing factor as it increases along with consumption of "western diet" and processed food in developed countries, where MS incidence is high.

Design/Methods After induction of EAE, C57BL/6 mice were fed on a HSD (4.0% NaCl) or normal diet (0.4% NaCl). Histological and immunological analyses were performed to dissect underlying mechanisms of action.

Results HSD led to earlier onset and aggravation of EAE as well as increased inflammatory infiltration of macrophages/microglia and T cells in spinal cord lesions (n=12 p.g., p<0.05). Analysis of gene expression revealed a shift towards Th17 helper T cell driven autoimmunity by HSD. Expression of IL-17A and the transcription factor RORgt, but not interferon-gamma or T-bet were elevated in the spleen (n=5-6 p.g. p<0.05) and spinal cord (n=5-6 p.g. p<0.05). In vitro, restimulation of MOG primed splenocytes from mice on a HSD led to increased expression of IL-17 and Th17 signature genes. In T cell polarization assays in vitro, increasing the culture NaCl concentration by 40 mM did not influence Th1 or Th2 polarization, but boosted Th17 cell polarization up to 10-fold (n=6-11 p.g. p<0.001). This process involved p38 dependent pathways in vitro and in vivo as demonstrated by pharmacological inhibition (SB202190, p<0.01) and genetic ablation in a conditional knockout mouse model (n=6 p.g., p<0.01).

Conclusions Our findings demonstrate that a high salt diet boosts Th17 responses thus exacerbating autoimmune neuroinflammation. Excess sodium uptake may constitute a new dietary factor possibly influencing complex autoimmune diseases like MS.

Authors/Disclosures
Ralf Linker (Uniklinik Erlangen) PRESENTER	Dr. Linker has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Linker has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer. The institution of Dr. Linker has received research support from Novartis. The institution of Dr. Linker has received research support from Biogen.
	No disclosure on file
	No disclosure on file
David A. Hafler, MD, FAAN (Yale University School of Medicine, Dept of Neurology)	Dr. Hafler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Hafler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genetech. Dr. Hafler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Hafler has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Joint Commission International.
	No disclosure on file
	No disclosure on file

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