The Geographic Distribution of Multiple Sclerosis: A Review

Ebers, G. C.; Sadovnick, A. Dessa

doi:10.1159/000110293

Cited by 113 publications

(56 citation statements)

References 27 publications

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“…The initiation and progression of a number of autoimmune diseases, including MS (5,36), are strongly suspected to arise secondary to virus infections. Therefore, determining the mechanisms by which infections lead to autoimmune sequelae is an area of great interest, and may provide important clues about the pathogenesis and regulation of autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

Endogenous presentation of self myelin epitopes by CNS-resident APCs in Theiler’s virus–infected mice

Katz-Levy¹,

Neville²,

Girvin³

et al. 1999

J. Clin. Invest.

132

127

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Section: Discussionmentioning

confidence: 99%

Endogenous presentation of self myelin epitopes by CNS-resident APCs in Theiler’s virus–infected mice

Katz-Levy¹,

Neville²,

Girvin³

et al. 1999

J. Clin. Invest.

132

127

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“…shows a striking gradient of increasing prevalence with increasing latitude (1). Worldwide studies have attributed this gradient to a strong link between low sunlight exposure and high MS risk (2)(3)(4)(5).…”

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

IL-10 Signaling Is Essential for 1,25-Dihydroxyvitamin D3-Mediated Inhibition of Experimental Autoimmune Encephalomyelitis

Spach¹,

Nashold

Dittel

et al. 2006

The Journal of Immunology

203

158

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Multiple sclerosis (MS) results from an aberrant, neuroantigen-specific, T cell-mediated autoimmune response. Because MS prevalence and severity decrease sharply with increasing sunlight exposure, and sunlight supports vitamin D3 synthesis, we proposed that vitamin D3 and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) may protect against MS. In support of this hypothesis, 1,25-(OH)2D3 strongly inhibited experimental autoimmune encephalomyelitis (EAE). This inhibition required lymphocytes other than the encephalitogenic T cells. In this study, we tested the hypothesis that 1,25-(OH)2D3 might inhibit EAE through the action of IL-10-producing regulatory lymphocytes. We report that vitamin D3 and 1,25-(OH)2D3 strongly inhibited myelin oligodendrocyte peptide (MOG35–55)-induced EAE in C57BL/6 mice, but completely failed to inhibit EAE in mice with a disrupted IL-10 or IL-10R gene. Thus, a functional IL-10-IL-10R pathway was essential for 1,25-(OH)2D3 to inhibit EAE. The 1,25-(OH)2D3 also failed to inhibit EAE in reciprocal, mixed bone marrow chimeras constructed by transferring IL-10-deficient bone marrow into irradiated wild-type mice and vice versa. Thus, 1,25-(OH)2D3 may be enhancing an anti-inflammatory loop involving hemopoietic cell-produced IL-10 acting on brain parenchymal cells and vice versa. If this interpretation is correct, and humans have a similar bidirectional IL-10-dependent loop, then an IL-10-IL-10R pathway defect could abrogate the anti-inflammatory and neuro-protective functions of sunlight and vitamin D3. In this way, a genetic IL-10-IL-10R pathway defect could interact with an environmental risk factor, vitamin D3 insufficiency, to increase MS risk and severity.

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“…Epidemiological studies have demonstrated that MS incidence typically follows a latitudinal gradient in both hemispheres. In Europe and North America, MS is more common in the northern regions, whereas MS is more prevalent in the southern part of Australia (4).…”

mentioning

confidence: 99%

UV radiation suppresses experimental autoimmune encephalomyelitis independent of vitamin D production

Becklund

Severson

Vang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

185

164

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Although the exact cause of multiple sclerosis (MS) is unknown, a number of genetic and environmental factors are thought to influence MS susceptibility. One potential environmental factor is sunlight and the subsequent production of vitamin D. A number of studies have correlated decreased exposure to UV radiation (UVR) and low serum 25-hydroxyvitamin D 3 [25(OH)D 3 ] levels with an increased risk for developing MS. Furthermore, both UVR and the active form of vitamin D, 1α,25-dihydroxyvitamin D 3 , suppress disease in the experimental autoimmune encephalomyelitis (EAE) animal model of MS. These observations led to the hypothesis that UVR likely suppresses disease through the increased production of vitamin D. However, UVR can suppress the immune system independent of vitamin D. Therefore, it is unclear whether UVR, vitamin D, or both are necessary for the putative decrease in MS susceptibility. We have probed the ability of UVR to suppress disease in the EAE model of MS and assessed the effect of UVR on serum 25(OH)D 3 and calcium levels. Our results indicate that continuous treatment with UVR dramatically suppresses clinical signs of EAE. Interestingly, disease suppression occurs with only a modest, transient increase in serum 25 (OH)D 3 levels. Further analysis demonstrated that the levels of 25(OH) D 3 obtained upon UVR treatment were insufficient to suppress EAE independent of UVR treatment. These results suggest that UVR is likely suppressing disease independent of vitamin D production, and that vitamin D supplementation alone may not replace the ability of sunlight to reduce MS susceptibility.calcium | immune | multiple sclerosis | sunlight

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The Geographic Distribution of Multiple Sclerosis: A Review

Cited by 113 publications

References 27 publications

Endogenous presentation of self myelin epitopes by CNS-resident APCs in Theiler’s virus–infected mice

Endogenous presentation of self myelin epitopes by CNS-resident APCs in Theiler’s virus–infected mice

IL-10 Signaling Is Essential for 1,25-Dihydroxyvitamin D3-Mediated Inhibition of Experimental Autoimmune Encephalomyelitis

UV radiation suppresses experimental autoimmune encephalomyelitis independent of vitamin D production

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