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Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis ‬

2017; National Academy of Sciences; Volume: 114; Issue: 9 Linguagem: Inglês

10.1073/pnas.1615783114

1091-6490

Manuel Zeitelhofer, Milena Z. Adzemovic, David Gómez-Cabrero, Petra Bergman, Sonja Hochmeister, Marie N’diaye, Atul Paulson, Stephan Ruhrmann, Malin Almgren, Jesper Tegnér, Tomas J. Ekström, André Ortlieb Guerreiro‐Cacais, Maja Jagodic,

Reproductive System and Pregnancy

Significance Vitamin D has been suggested to be associated with beneficial immunomodulation in autoimmune diseases. We demonstrate that the protective effect of vitamin D in an animal model of multiple sclerosis (MS) is linked to multiple signaling and metabolic pathways critical for T-cell activation and differentiation into pathogenic T helper (Th) 1 and Th17 subsets in vivo. This effect is mediated by epigenetic mechanisms as reflected by genome-wide reduction of DNA methylation and upregulation of microRNAs, with concomitant downregulation of their protein-coding target genes. Our data support the role of vitamin D in modulating risk for human disease, because orthologues of nearly 50% of MS candidate risk genes changed their expression in vivo in CD4+ T cells upon vitamin D supplementation.