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Thiamine deficiency promotes T cell infiltration in experimental autoimmune encephalomyelitis: the involvement of CCL2
Journal article   Peer reviewed

Thiamine deficiency promotes T cell infiltration in experimental autoimmune encephalomyelitis: the involvement of CCL2

Zhe Ji, Zhiqin Fan, Ying Zhang, Ronghuan Yu, Haihua Yang, Chenghua Zhou, Jia Luo and Zun-Ji Ke
The Journal of immunology (1950), Vol.193(5), pp.2157-2167
09/01/2014
DOI: 10.4049/jimmunol.1302702
PMCID: PMC4135011
PMID: 25063874

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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.
Animals Cell Movement - drug effects Cell Movement - immunology Cell Proliferation Chemokine CCL2 - immunology Encephalomyelitis, Autoimmune, Experimental - complications Encephalomyelitis, Autoimmune, Experimental - immunology Encephalomyelitis, Autoimmune, Experimental - pathology Lymph Nodes - immunology Lymph Nodes - pathology Mice Microglia - immunology Microglia - pathology Myelin-Oligodendrocyte Glycoprotein - immunology Myelin-Oligodendrocyte Glycoprotein - toxicity Peptide Fragments - immunology Peptide Fragments - toxicity Rats Spinal Cord - immunology Spinal Cord - pathology Spleen - immunology Spleen - pathology Th1 Cells - immunology Th1 Cells - pathology Th17 Cells - immunology Th17 Cells - pathology Thiamine Deficiency - complications Thiamine Deficiency - immunology Thiamine Deficiency - pathology

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