The influence of sodium on pathophysiology of multiple sclerosis

Neurological Sciences

Volumn 38, Issue 3, 2017, Pages 389-398

  Zostawa, Jacek ^a   Adamczyk, Jowita ^a   Sowa, Paweł ^a   Adamczyk Sowa, Monika ^a  

^a MEDICAL UNIVERSITY OF SILESIA   (Poland)

Author keywords

Environmental factors in MS; Multiple sclerosis; Sodium chloride intake; VGSCs

Indexed keywords

ADENOSINE TRIPHOSPHATASE (POTASSIUM SODIUM); ADENOSINE TRIPHOSPHATE; SODIUM CHLORIDE; VITAMIN D; VOLTAGE GATED SODIUM CHANNEL; SALT INTAKE;

DISEASE PREDISPOSITION; ENVIRONMENTAL FACTOR; HUMAN; MULTIPLE SCLEROSIS; NONHUMAN; OBESITY; PATHOPHYSIOLOGY; REVIEW; SALT INTAKE; SMOKING; SODIUM TRANSPORT; ULTRAVIOLET RADIATION; VITAMIN BLOOD LEVEL; VITAMIN SUPPLEMENTATION; ADVERSE EFFECTS; ANIMAL; ENVIRONMENTAL EXPOSURE; IMMUNOLOGY; MOUSE;

ANIMALS; ENVIRONMENTAL EXPOSURE; HUMANS; MICE; MULTIPLE SCLEROSIS; SODIUM CHLORIDE; SODIUM CHLORIDE, DIETARY;

EID: 85009247274     PISSN: 15901874     EISSN: 15903478     Source Type: Journal    
DOI: 10.1007/s10072-016-2802-8     Document Type: Review

References (147)

1. Moghadasi AN, Pourmand S, Sharifian M et al (2016) Behavioral neurology of multiple sclerosis and autoimmune encephalopathies. Neurol Clin 34(1):17–31
2. Mandia D, Ferraro OE, Nosari G et al (2014) Environmental factors and multiple sclerosis severity: a descriptive study. Int J Environ Res Public Health 11(6):6417–6432
3. Ascherio A, Munger KL, Lennette ET et al (2001) Epstein-Barr virus antibodies and risk of multiple sclerosis: a prospective study. JAMA 286(24):3083–3088
4. Farrell RA, Antony D, Wall GR et al (2009) Humoral immune response to EBV in multiple sclerosis is associated with disease activity on MRI. Neurology 73(1):32–38
5. Ramroodi N, Niazi AA, Sanadgol N et al (2013) Evaluation of reactive Epstein-Barr Virus (EBV) in Iranian patient with different subtypes of multiple sclerosis (MS). Braz J Infect Dis 17(2):156–163
6. Pierrot-Deseilligny C (2009) Clinical implications of a possible role of vitamin D in multiple sclerosis. J Neurol 256(9):1468–1479
7. Cline J (2012) Calcium and vitamin d metabolism, deficiency, and excess. Top Companion Anim Med 27(4):159–164
8. Holmøy T, Torkildsen Ø, Myhr KM et al (2012) Vitamin D supplementation and monitoring in multiple sclerosis: who, when and wherefore. Acta Neurol Scand Suppl 195:63–69
9. Steffensen LH, Brustad M, Kampman MT (2013) What is needed to keep persons with multiple sclerosis vitamin D-sufficient throughout the year? J Neurol 260(1):182–188
10. Kampman MT, Steffensen LH, Mellgren SI et al (2012) Effect of vitamin D3 supplementation on relapses, disease progression, and measures of function in persons with multiple sclerosis: exploratory outcomes from a double-blind randomised controlled trial. Mult Scler 18(8):1144–1151
11. Stein MS, Liu Y, Gray OM et al (2011) A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology 77(17):1611–1618
12. Hedström AK, Olsson T, Alfredsson L (2016) Smoking is a major preventable risk factor for multiple sclerosis. Mult Scler 22(8):1021–1026
13. Ramanujam R, Hedström AK, Manouchehrinia A et al (2015) Effect of smoking cessation on multiple sclerosis prognosis. JAMA Neurol 72(10):1117–1123
14. Kvistad SS, Myhr KM, Holmøy T et al (2015) Body mass index influence interferon-betatreatment response in multiple sclerosis. J Neuroimmunol 288:92–97
15. Sloka S, Silva C, Pryse-Phillips W et al (2011) A quantitative analysis of suspected environmental causes of MS. Can J Neurol Sci 38(1):98–105
16. Bäärnhielm M, Hedström AK, Kockum I et al (2012) Sunlight is associated with decreased multiple sclerosis risk: no interaction with human leukocyte antigen-DRB1*15. Eur J Neurol 19(7):955–962
17. Marrie RA (2004) Environmental risk factors in multiple sclerosis aetiology. Lancet Neurol 3(12):709–718
18. Pugliatti M, Sotgiu S, Rosati G (2002) The worldwide prevalence of multiple sclerosis. Clin Neurol Neurosurg 104(3):182–191
19. Munger KL, Levin LI, O’Reilly EJ et al (2011) Anti-Epstein-Barr virus antibodies as serological markers of multiple sclerosis: a prospective study among United States military personnel. Mult Scler 17(10):1185–1193
20. Villoslada P, Juste C, Tintore M et al (2003) The immune response against herpesvirus is more prominent in the early stages of MS. Neurology 60(12):1944–1948
21. Yea C, Tellier R, Chong P et al (2013) Canadian pediatric demyelinating disease network. Epstein-Barr virus in oral shedding of children with multiple sclerosis. Neurology 81(16):1392–1399
22. Buljevac D, Flach HZ, Hop WC et al (2002) Prospective study on the relationship between infections and multiple sclerosis exacerbations. Brain 125(Pt5):952–960
23. Versini M, Jeandel PY, Rosenthal E et al (2014) Obesity in autoimmune diseases: not a passive bystander. Autoimmun Rev 13(9):981–1000
24. Cao H (2014) Adipocytokines in obesity and metabolic disease. J Endocrinol 220(2):T47–T59
25. Oliveira SR, Simão AN, Kallaur AP et al (2014) Disability in patients with multiple sclerosis: influence of insulin resistance, adiposity, and oxidative stress. Nutrition 30(3):268–273
26. Simpson S Jr, Blizzard L, Otahal P et al (2011) Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis. J Neurol Neurosurg Psychiatry 82(10):1132–1141
27. Harbo HF, Utsi E, Lorentzen AR et al (2007) Low frequency of the disease-associated DRB1*15-DQB1*06 haplotype may contribute to the low prevalence of multiple sclerosis in Sami. Tissue Antigens 69(4):299–304
28. Kingwell E, Marriott JJ, Jetté N et al (2013) Incidence and prevalence of multiple sclerosis in Europe: a systematic review. BMC Neurol 13:128
29. Kantarci O, Wingerchuk D (2006) Epidemiology and natural history of multiple sclerosis: new insights. Curr Opin Neurol 19(3):248–254
30. Coo H, Aronson KJ (2004) A systematic review of several potential non-genetic risk factors for multiple sclerosis. Neuroepidemiology 23(1–2):1–12
31. Smolders J, Damoiseaux J, Menheere P et al (2008) Vitamin D as an immune modulator in multiple sclerosis, a review. J Neuroimmunol 194(1–2):7–17
32. Pantzaris MC, Loukaides GN, Ntzani EE et al (2013) A novel oral nutraceutical formula of omega-3 and omega-6 fatty acids with vitamins (PLP10) in relapsing remitting multiple sclerosis: a randomised, double-blind, placebo-controlled proof-of-concept clinical trial. BMJ Open 3(4):e002170
33. Torkildsen O, Wergeland S, Bakke S et al (2012) ω-3 fatty acid treatment in multiple sclerosis (OFAMS Study): a randomized, double-blind, placebo-controlled trial. Arch Neurol 69(8):1044–1051
34. Khalili M, Azimi A, Izadi V et al (2014) Does lipoic acid consumption affect the cytokine profile in multiple sclerosis patients: a double-blind, placebo-controlled, randomized clinical trial. Neuroimmunomodulation 21(6):291–296
35. Vergelli M, Olivotto J, Castigli E et al (1997) Immunosuppressive activity of 13-cis-retinoic acid in rats: aspects of pharmacokinetics and pharmacodynamics. Immunopharmacology 37(2–3):191–197
36. Hall JA, Grainger JR, Spencer SP et al (2011) The role of retinoic acid in tolerance and immunity. Immunity 35(1):13–22
37. Bitarafan S, Saboor-Yaraghi A, Sahraian MA et al (2016) Effect of vitamin A supplementation on fatigue and depression in multiple sclerosis patients: a double-blind placebo-controlled clinical trial. Iran J Allergy Asthma Immunol 15(1):13–19
38. Storoni M, Plant GT (2015) The therapeutic potential of the ketogenic diet in treating progressive multiple sclerosis. Mult Scler Int 2015:681289
39. Allen BG, Bhatia SK, Anderson CM et al (2014) Ketogenic diets as an adjuvant cancer therapy: history and potential mechanism. Redox Biol 2:963–970
40. Kim do Y, Hao J, Liu R et al (2012) Inflammation-mediated memory dysfunction and effects of a ketogenic diet in a murine model of multiple sclerosis. PLoS One 7(5):e35476
41. Malin SK, Cotugna N, Fang CS (2008) Effect of creatine supplementation on muscle capacity in individuals with multiple sclerosis. J Diet Suppl 5(1):20–32
42. Swank RL, Goodwin J (2003) Review of MS patient survival on a Swank low saturated fat diet. Nutrition 19(2):161–162
43. Riccio P, Rossano R (2015) Nutrition facts in multiple sclerosis. ASN Neuro 7(1):1759091414568185. doi:10.1177/1759091414568185
44. Plemel JR, Juzwik CA, Benson CA et al (2015) Over-the-counter anti-oxidant therapies for use in multiple sclerosis: a systematic review. Mult Scler 21(12):1485–1495
45. Abdolahi M, Yavari P, Honarvar NM et al (2015) Molecular mechanisms of the action of vitamin A in Th17/Treg axis in multiple sclerosis. J Mol Neurosci 57(4):605–613
46. Bitarafan S, Saboor-Yaraghi A, Sahraian MA et al (2015) Impact of vitamin A supplementation on disease progression in patients with multiple sclerosis. Arch Iran Med 18(7):435–440
47. Hille B (1978) Ionic channels in excitable membranes. Current problems and biophysical approaches. Biophys J 22(2):283–294
48. Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 117:500–544
49. Barres BA, Chun LL, Corey DP (1990) Ion channels in vertebrate glia. Annu Rev Neurosci 13:441–474
50. Gautron S, Dos Santos G, Pinto-Henrique D et al (1992) The glial voltage-gated sodium channel: cell- and tissue-specific mRNA expression. Proc Natl Acad Sci USA 89(15):7272–7276
51. Gosling M, Harley SL, Turner RJ et al (1998) Human saphenous vein endothelial cells express a tetrodotoxin-resistant, voltage-gated sodium current. J Biol Chem 273(33):21084–21090
52. + channels: multiplicity of expression, plasticity, functional implications and pathophysiological aspects. Eur Biophys J 33(3):180–193
53. Káradóttir R, Hamilton NB, Bakiri Y et al (2008) Spiking and nonspiking classes of oligodendrocyte precursor glia in CNS white matter. Nat Neurosci 11(4):450–456
54. Zhao P, Barr TP, Hou Q et al (2008) Voltage-gated sodium channel expression in rat and human epidermal keratinocytes: evidence for a role in pain. Pain 139(1):90–105
55. Lopez-Santiago LF, Meadows LS, Ernst SJ et al (2007) Sodium channel Scn1b null mice exhibit prolonged QT and RR intervals. J Mol Cell Cardiol 43:636–647
56. +-channel beta1 subunit gene SCN1B. Nat Genet 19:366–370
57. Audenaert D, Claes L, Ceulemans B et al (2003) A deletion in SCN1B is associated with febrile seizures and early-onset absence epilepsy. Neurology 61:854–856
58. Scheffer IE, Harkin LA, Grinton BE et al (2007) Temporal lobe epilepsy and GEFS+ phenotypes associated with SCN1B mutations. Brain 130(Pt 1):100–109
59. Lopez-Santiago LF, Pertin M, Morisod X et al (2006) Sodium channel beta2 subunits regulate tetrodotoxin-sensitive sodium channels in small dorsal root ganglion neurons and modulate the response to pain. J Neurosci 26:7984–7994
60. Cummins TR, Sheets PL, Waxman SG (2007) The roles of sodium channels in nociception: implications for mechanisms of pain. Pain 131:243–257
61. Fontaine B, Khurana TS, Hoffman EP et al (1990) Hyperkalemic periodic paralysis and the adult muscle sodium channel alpha-subunit gene. Science 250:1000–1002
62. Waxman SG (2007) Channel, neuronal and clinical function in sodium channelopathies: from genotype to phenotype. Nat Neurosci 10:405–409
63. Dichgans M, Freilinger T, Eckstein G et al (2005) Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine. Lancet 366:371–377
64. Waxman SG (2006) Axonal conduction and injury in multiple sclerosis: the role of sodium channels. Nat Rev Neurosci 7:932–941
65. Fraser SP, Diss JK, Chioni AM et al (2005) Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis. Clin Cancer Res 11:5381–5389
66. + channels: potential for beta subunits as therapeutic targets. Expert Opin Ther Targets 12(9):1191–1203
67. + channels in cellular migration: regulation of central nervous system development and potentiation of invasive cancers. Neuroscientist 14(6):571–583
68. Roy ML, Narahashi T (1992) Differential properties of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons. J Neurosci 12(6):2104–2111
69. 2+ currents of acutely isolated adult rat nodose ganglion cells. J Neurophysiol 55(3):527–539
70. Sun LH, Yan ML, Hu XL et al (2015) MicroRNA-9 induces defective trafficking of Nav1.1 and Nav1.2 by targeting Navβ2 protein coding region in rat with chronic brain hypoperfusion. Mol Neurodegener 10:36
71. Ogiwara I, Miyamoto H, Morita N et al (2007) Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. J Neurosci 27(22):5903–5914
72. Catterall WA, Kalume F, Oakley JC (2010) NaV1.1 channels and epilepsy. J Physiol 588(Pt 11):1849–1859
73. Howell KB, McMahon JM, Carvill GL et al (2015) SCN2A encephalopathy: a major cause of epilepsy of infancy with migrating focal seizures. Neurology 85(11):958–966
74. Gazina EV, Leaw BT, Richards KL et al (2015) ‘Neonatal’ Nav1.2 reduces neuronal excitability and affects seizure susceptibility and behaviour. Hum Mol Genet 24(5):1457–1468
75. +channels in pancreatic α-cells has antidiabetic effects. Diabetes 63(10):3545–3556
76. Lin CR, Chen KH, Yang CH et al (2014) Intrathecal miR-183 delivery suppresses mechanical allodynia in mononeuropathic rats. Eur J Neurosci 39(10):1682–1689
77. Tan AM, Samad OA, Dib-Hajj SD et al (2015) Virus-mediated knockdown of Nav1.3 in dorsal root ganglia of STZ-induced diabetic rats alleviates tactile allodynia. Mol Med 21:544–552
78. Zang Y, He XH, Xin WJ et al (2010) Inhibition of NF-kappaB prevents mechanical allodynia induced by spinal ventral root transection and suppresses the re-expression of Nav1.3 in DRG neurons in vivo and in vitro. Brain Res 1363:151–158
79. Bissay V, Van Malderen SC, Keymolen K et al (2016) SCN4A variants and Brugada syndrome: phenotypic and genotypic overlap between cardiac and skeletal muscle sodium channelopathies. Eur J Hum Genet 24(3):400–407
80. Cannon SC (2015) Channelopathies of skeletal muscle excitability. Compr Physiol 5(2):761–790
81. Nelson M, Yang M, Millican-Slater R et al (2015) Nav1.5 regulates breast tumor growth and metastatic dissemination in vivo. Oncotarget 6(32):32914–32929
82. Mohammed FH, Khajah MA, Yang M et al (2016) Blockade of voltage-gated sodium channels inhibits invasion of endocrine-resistant breast cancer cells. Int J Oncol 48(1):73–83
83. Musa H, Kline CF, Sturm AC et al (2015) SCN5A variant that blocks fibroblast growth factor homologous factor regulation causes human arrhythmia. Proc Natl Acad Sci USA 112(40):12528–12533
84. Tan BY, Yong RY, Barajas-Martinez H et al (2016) A Brugada syndrome proband with compound heterozygote SCN5A mutations identified from a Chinese family in Singapore. Europace 18(6):897–904
85. + channels in human endothelial cells: modulation of vascular endothelial growth factor (VEGF) signaling. J Biol Chem 286(19):16846–16860
86. O’Brien JE, Meisler MH (2013) Sodium channel SCN8A (Nav1.6): properties and de novo mutations in epileptic encephalopathy and intellectual disability. Front Genet 4:213
87. Hernandez-Plata E, Ortiz CS, Marquina-Castillo B et al (2012) Overexpression of NaV 1.6 channels is associated with the invasion capacity of human cervical cancer. Int J Cancer 130(9):2013–2023
88. Fertleman CR, Ferrie CD, Aicardi J et al (2007) Paroxysmal extreme pain disorder (previously familial rectal pain syndrome). Neurology 69(6):586–595
89. Suy S, Hansen TP, Auto HD et al. (2012) Expression of voltage-gated sodium channel Na(v)1.8 in human prostate cancer is associated with high histological grade. J Clin Exp Oncol. doi:10.4172/2324-9110.1000102
90. Han C, Huang J, Waxman SG (2016) Sodium channel Nav1.8: emerging links to human disease. Neurology 86(5):473–483
91. Roostaei T, Sadaghiani S, Park MT et al (2016) Channelopathy-related SCN10A gene variants predict cerebellar dysfunction in multiple sclerosis. Neurology 86(5):410–417
92. Woods CG, Babiker MO, Horrocks I et al (2015) The phenotype of congenital insensitivity to pain due to the NaV1.9 variant p. L811P. Eur J Hum Genet 23(10):1434
93. Leipold E, Hanson-Kahn A, Frick M et al (2015) Cold-aggravated pain in humans caused by a hyperactive NaV1.9 channel mutant. Nat Commun 6:10049
94. Xu W, Hong SJ, Zhong A et al (2015) Sodium channel Nax is a regulator in epithelial sodium homeostasis. Sci Transl Med 7(312):312ra177
95. Noda M, Hiyama TY (2015) Sodium sensing in the brain. Pflug Arch 467(3):465–474
96. Scheffer IE, Harkin LA, Grinton BE et al (2007) Temporal lobe epilepsy and GEFS+ phenotypes associated with SCN1B mutations. Brain 130(Pt 1):100–109
97. Watanabe H, Darbar D, Kaiser DW et al (2009) Mutations in sodium channel beta1- and beta2-subunits associated with atrial fibrillation. Circ Arrhythm Electrophysiol 2:268–275
98. Roger S, Rollin J, Barascu A et al (2007) Voltage-gated sodium channels potentiate the invasive capacities of human non-small-cell lung cancer cell lines. Int J Biochem Cell Biol 39:774–786
99. + channel beta2 subunits is neuroprotective in a mouse model of multiple sclerosis. Mol Cell Neurosci 40(2):143–155
100. Oyama F, Miyazaki H, Sakamoto N et al (2006) Sodium channel beta4 subunit: down-regulation and possible involvement in neuritic degeneration in Huntington’s disease transgenic mice. J Neurochem 98(2):518–529
101. Isom LL, De Jongh KS, Patton DE et al (1992) Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel. Science 256(5058):839–842
102. Isom LL, Ragsdale DS, De Jongh KS et al (1995) Structure and function of the beta 2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif. Cell 83(3):433–442
103. Morgan K, Stevens EB, Shah B et al (2003) beta 3: an additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channel gating with distinct kinetics. Proc Natl Acad Sci USA 97(5):2308–2313
104. Yu FH, Westenbroek RE, Silos-Santiago I et al (2003) Sodium channel beta4, a new disulfide-linked auxiliary subunit with similarity to beta2. J Neurosci 23(20):7577–7585
105. Black JA, Westenbroek R, Ransom BR et al (1994) Type II sodium channels in spinal cord astrocytes in situ: immunocytochemical observations. Glia 12:219–227
106. Reese KA, Caldwell JH (1999) Immunocytochemical localization of NaCh6 in cultured spinal cord astrocytes. Glia 26:92–96
107. + channel mRNA and protein in spinal cord astrocytes. Glia 23:200–208
108. Barres BA, Chun LL, Corey DP (1989) Glial and neuronal forms of the voltage-dependent sodium channel: characteristics and cell-type distribution. Neuron 2:1375–1388
109. Herzog RI, Liu C, Waxman SG et al (2003) Calmodulin binds to the C terminus of sodium channels Nav1.4 and Nav1.6 and differentially modulates their functional properties. J Neurosci 23:8261–8270
110. Kapoor R (2008) Sodium channel blockers and neuroprotection in multiple sclerosis using lamotrigine. J Neurolog Sci 274(1–2):54–56
111. 2+ release in rat optic nerve during in vitro chemical ischemia. J Neurosci 25:9960–9967
112. Waxman SG (2008) Mechanisms of disease: sodium channels and neuroprotection in multiple sclerosis current status. Nat Clin Pract Neurol 4(3):159–169
113. 2+ exchange. Glia 62(7):1162–1175
114. Bechtold DA, Kapoor R, Smith KJ (2004) Axonal protection using flecainide in experimental autoimmune encephalomyelitis. Ann Neurol 55(5):607–616
115. Morsali D, Bechtold D, Lee W et al (2013) Safinamide and flecainide protect axons and reduce microglial activation in models of multiple sclerosis. Brain 136(Pt 4):1067–1082
116. Lo AC, Black JA, Waxman SG (2002) Neuroprotection of axons with phenytoin in experimental allergic encephalomyelitis. Neuroreport 13:1909–1912
117. Bechtold DA, Miller SJ, Dawson AC et al (2006) Axonal protection achieved in a model of multiple sclerosis using lamotrigine. J Neurol 253:1542–1551
118. Craner MJ, Damarjian TG, Liu S et al (2005) Sodium channels contribute to microglia/macrophage activation and function in EAE and MS. Glia 49(2):220–229
119. Counihan TJ, Duignan JA, Gormley G et al (2014) Does long-term partial sodium channel blockade alter disease progression in MS? Evidence from a retrospective study. Ir J Med Sci 183(1):117–121
120. Gnanapavan S, Grant D, Morant S et al (2013) Biomarker report from the phase II lamotrigine trial in secondary progressive MS- neurofilament as a surrogate of disease progression. PLoS One 8(8):e70019
121. Kapoor R, Furby J, Hayton T et al (2010) Lamotrigine for neuroprotection in secondary progressive multiple sclerosis: a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet Neurol 9(7):681–688
122. Kleinewietfeld M, Manzel A, Titze J et al (2013) Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature 496(7446):518–522
123. McGuire S (2010) Institute of Medicine. 2010. Strategies to reduce sodium intake in the United States. The National Academies Press, Washington. Adv Nutr 1:49–50
124. Appel LJ, Frohlich ED, Hall JE et al (2011) The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke: a call to action from the American Heart Association. Circulation 123:1138–1143
125. Brown IJ, Tzoulaki I, Candeias V et al (2009) Salt intakes around the world: implications for public health. Int J Epidemiol 38:791–813
126. Junger WG, Liu FC, Loomis WH et al (1994) Hypertonic saline enhances cellular immune function. Circ Shock 42:190–196
127. Machnik A, Neuhofer W, Jantsch et al (2009) Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat Med 15(5):545–552
128. Korn T, Bettelli E, Oukka M et al (2009) IL-17 and Th17 Cells. Annu Rev Immunol 27:485–517
129. Ghoreschi K, Laurence A, Yang XP et al (2010) Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling. Nature 467:967–971
130. Wu C, Yosef N, Thalhamer T et al (2013) Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature 496(7446):513–517
131. Codarri L, Gyülvészi G, Tosevski V et al (2011) RORgammat drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol 12:560–567
132. El-Behi M, Ciric B, Dai H et al (2011) The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol 12:568–575
133. Reboldi A, Coisne C, Baumjohann D et al (2009) C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nat Immunol 10:514–523
134. Go WY, Liu X, Roti MA et al (2004) NFAT5/TonEBP mutant mice define osmotic stress as acritical feature of the lymphoid microenvironment. Proc Natl Acad Sci USA 101:10673–10678
135. Farez MF, Fiol MP, Gaitán MI et al (2015) Sodium intake is associated with increased disease activity in multiple sclerosis. J Neurol Neurosurg Psychiatry 86(1):26–31
136. Fulgoni VL 3rd (2007) Limitations of data on fluid intake. J Am Coll Nutr 26(5 Suppl):588S–591S
137. Han MH, Hwang SI, Roy DB et al (2008) Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets. Nature 451(7182):1076–1081
138. Goodfriend TL, Elliott ME, Catt KJ (1996) Angiotensin receptors and their antagonists. N Engl J Med 334:1649–1654
139. Stegbauer J, Lee DH, Seubert S et al (2009) Role of the renin-angiotensin system in autoimmune inflammation of the central nervous system. Proc Natl Acad Sci USA 106:14942–14947
140. Maillard P, Seshadri S, Beiser A et al (2012) Effects of systolic blood pressure on white-matter integrity in young adults in the Framingham Heart Study: a cross-sectional study. Lancet Neurol 11:1039–1047
141. Platten M, Youssef S, Hur EM et al (2009) Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity. Proc Natl Acad Sci USA 106(35):14948–14953
142. Hucke S, Eschborn M, Liebmann M et al (2016) Sodium chloride promotes pro-inflammatory macrophage polarization thereby aggravating CNS autoimmunity. J Autoimmun 67:90–101
143. Yi B, Titze J, Rykova M et al (2015) Effects of dietary salt levels on monocytic cells and immune responses in healthy human subjects: a longitudinal study. Transl Res 166(1):103–110
144. Jörg S, Kissel J, Manzel A et al (2016) High salt drives Th17 responses in experimental autoimmune encephalomyelitis without impacting myeloid dendritic cells. Exp Neurol 279:212–222
145. Krementsov DN, Case LK, Hickey WF et al (2015) Exacerbation of autoimmune neuroinflammation by dietary sodium is genetically controlled and sex specific. FASEB J 29(8):3446–3457
146. Zhou X, Zhang L, Ji WJ et al (2013) Variation in dietary salt intake induces coordinated dynamics of monocyte subsets and monocyte-platelet aggregates in humans: implications in end organ inflammation. In: Zirlik A (ed) PLoS One 8(4):e60332
147. Hernandez AL, Kitz A, Wu C et al (2015) Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells. J Clin Investig 125(11):4212–4222