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 C-C Chemokine Ligand 2 (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) peptide 35–55 with/without TD. TD aggravated the development of EAE which was indicated by clinical scores and pathological 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 Th-1 and Th-17 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 pathological inflammation.

The effects of diet on the severity of central nervous system disease: One part of lab-to-lab variability

“…Various vitamins have also been examined for their effects on EAE [24,25]. One study showed that vitamin D3 supplementation significantly inhibited the incidence and severity of MBP-induced EAE in female B10.PL mice, compared to unsupplemented female mice and male mice with or without supplementation, a difference thought to be due to a gender difference in vitamin D3 metabolism within the CNS [24].…”

Comment on “Thiamine Deficiency Promotes T Cell Infiltration in Experimental Autoimmune Encephalomyelitis: The Involvement of CCL2”

“…However, TD-induced neuroinflammation not only involves astrocytes, but also neurons, microglia, and endothelia cells. As previously demonstrated, TD produces a mild, chronic impairment of oxidative metabolism and reduced activities of the thiamine-dependent mitochondrial enzymes (1). TD causes regionally selective neuronal death and activation of astrocytes, microglia, and endothelial cells, which are also observed in various neurodegenerative disorders (1).…”

“…As previously demonstrated, TD produces a mild, chronic impairment of oxidative metabolism and reduced activities of the thiamine-dependent mitochondrial enzymes (1). TD causes regionally selective neuronal death and activation of astrocytes, microglia, and endothelial cells, which are also observed in various neurodegenerative disorders (1). TD induces a time-dependent chronic impairment of oxidative metabolism that initiates a cascade leading to selective neuronal loss that occurs first in the submedial thalamic nucleus in mice (2) and the mammillary bodies, the periaqueductal area, the periventricular region of the third ventricle, and the paramedian thalamic nuclei in humans (3).…”

“…Comment on "Thiamine Deficiency Promotes T Cell Infiltration in Experimental Autoimmune Encephalomyelitis: The Involvement of CCL2" Z he Ji et al (1) reported that experimental autoimmune encephalomyelitis (induced either by MOG peptide immunization or by MOG-immune T cell transfer) was more severe in mice with thiamine deficiency (TD) than in mice without TD, and concluded that TD influences neuroinflammation by upregulating the chemokine CCL2 and its receptor CCR2. We note that astrocytes (five times more abundant than neurons and major orchestrators of neuroinflammation) are particularly susceptible to TD.…”

Is there a Link between Vitamin B and Multiple Sclerosis?

“…In a mouse model of MS, experimental autoimmune encephalomyelitis (EAE) induced by, myelin oligodendrocyte glycoprotein encephalitogenic peptide, MOG35-55, the disease severity is exacerbated in thiamine deficient mice compared to non-thiamine deficient mice. The deficient mice showed pathologic alterations in the spinal cord, microglial activation and increased Th1 and Th17 cell infiltration and increased expression of chemokine, CCL2, and its receptor in the spinal cord [23]. Thus, there is preliminary evidence that suggests some potential role of thiamine in MS, however these need to be substantiated in larger studies.…”