Proceedings of the National Academy of Sciences · 2017 · 103 citations · 65 references
Life SciencesGeneticsImmunologyAutoimmunityEpigeneticsNeuroimmunologyAutoimmune Disease Susceptibility GenesAutoimmune DiseasesMultiple SclerosisVitamin DVitamin D MetabolismVitamin PhysiologyCd4 Positive T CellsCd4 T Cell ActivationExperimental Autoimmune EncephalomyelitisHuman Disease ModelsMultiple Sclerosis ImmunopathogenesisMultiple Sclerosis ImmunopathologyNutritional ImmunomodulationPathogenic T Helper Cell Differentiation
) up-regulation of noncoding RNAs, including microRNAs, with concomitant down-regulation of their protein-coding target RNAs involved in T-cell activation and differentiation. We further demonstrate that treatment of myelin-specific T cells with vitamin D reduces frequency of Th1 and Th17 cells, down-regulates genes in key signaling pathways and epigenetic machinery, and impairs their ability to transfer EAE. Finally, orthologs of nearly 50% of candidate MS risk genes and 40% of signature genes of myelin-reactive T cells in MS changed their expression in vivo in EAE upon supplementation, supporting the hypothesis that vitamin D may modulate risk for developing MS.
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