The multiple sclerosis susceptibility genes TAGAP and IL2RA are regulated by vitamin D in CD4+ T cells

多发性硬化症易感基因 TAGAP 和 IL2RA 受 CD4+ T 细胞中的维生素 D 调控

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作者:T Berge, I S Leikfoss, I S Brorson, S D Bos, C M Page, M W Gustavsen, A Bjølgerud, T Holmøy, E G Celius, J Damoiseaux, J Smolders, H F Harbo, A Spurkland

Abstract

Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system that develops in genetically susceptible individuals. The majority of the MS-associated gene variants are located in genetic regions with importance for T-cell differentiation. Vitamin D is a potent immunomodulator, and vitamin D deficiency has been suggested to be associated with increased MS disease susceptibility and activity. In CD4+ T cells, we have analyzed in vitro vitamin D responsiveness of genes that contain an MS-associated single-nucleotide polymorphism (SNP) and with one or more vitamin D response elements in their regulatory regions. We identify IL2RA and TAGAP as novel vitamin D target genes. The vitamin D response is observed in samples from both MS patients and controls, and is not dependent on the genotype of MS-associated SNPs in the respective genes.

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