title: High salt drives Th17 responses in experimental autoimmune encephalomyelitis without impacting myeloid dendritic cells.
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.
authors.affiliation: Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Jörg
authors.affiliation: Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Kissel
authors.affiliation: Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Manzel
authors.affiliation: Translational Immunology, Medical Faculty Carl Gustav Carus, Dresden, Germany; VIB Laboratory of Translational Immunomodulation, Hasselt University, Diepenbeek, Belgium.
authors.forename: Markus
authors.initials: M
authors.lastname: Kleinewietfeld
authors.affiliation: Department of Neurology, Ruhr-University Bochum, Germany.
authors.forename: Aiden
authors.initials: A
authors.lastname: Haghikia
authors.affiliation: Department of Neurology, Ruhr-University Bochum, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.affiliation: Experimental and Clinical Research Center & Max-Delbrück Center Berlin, Germany.
authors.forename: Dominik N
authors.initials: DN
authors.lastname: Müller
authors.affiliation: Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, Germany. Electronic address: ralf.linker@uk-erlangen.de.
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Linker
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects*; D004032:Diet; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects; D012965:Sodium Chloride / Q000494:pharmacology*; D012982:Sodium, Dietary / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D058504:Th17 Cells / Q000187:drug effects*
chemical_list: D016207:Cytokines; C098680:Il17a protein, mouse; D020381:Interleukin-17; D012982:Sodium, Dietary; D012965:Sodium Chloride
keywords: Co-culture; Experimental autoimmune encephalomyelitis; High-dietary salt; Myeloid dendritic cells; Sodium chloride