title: Thiamine deficiency promotes T cell infiltration in experimental autoimmune encephalomyelitis: the involvement of CCL2.
abstract: Multiple sclerosis (MS) is a complex multifactorial disease that results from the interplay between environmental factors and a susceptible genetic background. Experimental autoimmune encephalomyelitis (EAE) has been widely used to investigate the mechanisms underlying MS pathogenesis. Chemokines, such as CCL2, are involved in the development of EAE. We have previously shown that thiamine deficiency (TD) induced CCL2 in neurons. We hypothesized that TD may affect the pathogenesis of EAE. In this study, EAE was induced in C57BL/6J mice by the injection of myelin oligodendroglial glycoprotein (MOG) peptides 35-55 with or without TD. TD aggravated the development of EAE, which was indicated by clinical scores and pathologic alterations in the spinal cord. TD also accelerated the development of EAE in an adoptive transfer EAE model. TD caused microglial activation and a drastic increase (up 140%) in leukocyte infiltration in the spinal cord of the EAE mice; specifically, TD increased Th1 and Th17 cells. TD upregulated the expression of CCL2 and its receptor CCR2 in the spinal cord of EAE mice. Cells in peripheral lymph node and spleen isolated from MOG-primed TD mice showed much stronger proliferative responses to MOG. CCL2 stimulated the proliferation and migration of T lymphocytes in vitro. Our results suggested that TD exacerbated the development of EAE through activating CCL2 and inducing pathologic inflammation.
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
authors: Zhe
authors: Z
authors: Ji
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
authors: Zhiqin
authors: Z
authors: Fan
authors: Shanghai Clinical Center, Chinese Academy of Sciences/Shanghai Xuhui Central Hospital, Shanghai 200031, China;
authors: Ying
authors: Y
authors: Zhang
authors: Shanghai Clinical Center, Chinese Academy of Sciences/Shanghai Xuhui Central Hospital, Shanghai 200031, China;
authors: Ronghuan
authors: R
authors: Yu
authors: Shanghai Clinical Center, Chinese Academy of Sciences/Shanghai Xuhui Central Hospital, Shanghai 200031, China;
authors: Haihua
authors: H
authors: Yang
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
authors: Chenghua
authors: C
authors: Zhou
authors: Department of Molecular and Biochemical Pharmacology, University of Kentucky College of Medicine, Lexington, KY 40536; and zunjike@yahoo.com jialuo888@uky.edu.
authors: Jia
authors: J
authors: Luo
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China zunjike@yahoo.com jialuo888@uky.edu.
authors: Zun-Ji
authors: ZJ
authors: Ke
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D017628:Microglia / Q000276:immunology / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology / Q000633:toxicity; D010446:Peptide Fragments / Q000276:immunology / Q000633:toxicity; D051381:Rats; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology; D013832:Thiamine Deficiency / Q000150:complications / Q000276:immunology* / Q000473:pathology
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)