Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis .
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Zeitelhofer M, Adzemovic MZ, Gomez-Cabrero D, Bergman P, Hochmeister S, N'diaye M, Paulson A, Ruhrmann S, Almgren M, Tegnér JN, Ekström TJ, Guerreiro-Cacais AO, Jagodic M
Proc. Natl. Acad. Sci. U.S.A. 114 (9) E1678-E1687 [2017-02-28; online 2017-02-14]
Vitamin D exerts multiple immunomodulatory functions and has been implicated in the etiology and treatment of several autoimmune diseases, including multiple sclerosis (MS). We have previously reported that in juvenile/adolescent rats, vitamin D supplementation protects from experimental autoimmune encephalomyelitis (EAE), a model of MS. Here we demonstrate that this protective effect associates with decreased proliferation of CD4+ T cells and lower frequency of pathogenic T helper (Th) 17 cells. Using transcriptome, methylome, and pathway analyses in CD4+ T cells, we show that vitamin D affects multiple signaling and metabolic pathways critical for T-cell activation and differentiation into Th1 and Th17 subsets in vivo. Namely, Jak/Stat, Erk/Mapk, and Pi3K/Akt/mTor signaling pathway genes were down-regulated upon vitamin D supplementation. The protective effect associated with epigenetic mechanisms, such as (
PubMed 28196884
DOI 10.1073/pnas.1615783114
Crossref 10.1073/pnas.1615783114
pii: 1615783114
pmc: PMC5338504