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High salt drives Th17 responses in experimental autoimmune encephalomyelitis without impacting myeloid dendritic cells

Item Type:Article
Title:High salt drives Th17 responses in experimental autoimmune encephalomyelitis without impacting myeloid dendritic cells
Creators Name:Jörg, S. and Kissel, J. and Manzel, A. and Kleinewietfeld, M. and Haghikia, A. and Gold, R. and Müller, D.N. and Linker, R.A.
Abstract:Recently, we have shown that high dietary salt intake aggravates T helper cell (Th) 17 responses and neuroinflammation. Here, we employed in vitro assays for myeloid dendritic cell (mDC) maturation, DC cytokine production, T cell activation and ex vivo analyses in murine experimental autoimmune encephalomyelitis (EAE) to investigate whether the salt effect on Th17 cells is further mediated through DCs in vivo. In cell culture, an excess of 40mM sodium chloride did neither affect the generation, maturation nor the function of DCs, but, in different assays, significantly increased Th17 differentiation. During the initiation phase of MOG35-55 EAE, we did not observe altered DC frequencies or co-stimulatory capacities in lymphoid organs, while IL-17A production and Th17 cells in the spleen were significantly increased. Complementary ex vivo analyses of the spinal cord during the effector phase of EAE showed increased frequencies of Th17 cells, but did not reveal differences in phenotypes of CNS invading DCs. Finally, adaption of transgenic mice harboring a MOG specific T cell receptor to a high-salt diet led to aggravated clinical disease only after active immunization. Wild-type mice adapted to a high-salt diet in the effector phase of EAE, bypassing the priming phase of T cells, only displayed mildly aggravated disease. In summary, our data argue for a direct effect of NaCl on Th17 cells in neuroinflammation rather than an effect primarily exerted via DCs. These data may further fuel our understanding on the dietary impact on different immune cell subsets in autoimmune diseases, such as multiple sclerosis.
Keywords:Sodium Chloride, Myeloid Dendritic Cells, Co-Culture, High-Dietary Salt, Experimental Autoimmune Encephalomyelitis, Animals, Mice
Source:Experimental Neurology
Publisher:Elsevier / Academic Press
Page Range:212-222
Date:May 2016
Additional Information:Copyright © 2016 Published by Elsevier Inc.
Official Publication:https://doi.org/10.1016/j.expneurol.2016.03.010
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