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SHR Neuro Krebs Kardio Lipid

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.
Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis ‬.
Proc Natl Acad Sci U S A. 2017; 114(9):E1678-E1687 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Hochmeister Sonja
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Number of Figures: 10
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Abstract:
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 (i) changed levels of enzymes involved in establishment and maintenance of epigenetic marks, i.e., DNA methylation and histone modifications; (ii) genome-wide reduction of DNA methylation, and (iii) 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.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
CD4-Positive T-Lymphocytes - drug effects
Cell Differentiation - drug effects
Cell Proliferation - drug effects
Down-Regulation - drug effects
Encephalomyelitis, Autoimmune, Experimental - drug therapy
Epigenesis, Genetic - drug effects
Genomics - methods
Lymphocyte Activation - drug effects
Multiple Sclerosis - drug therapy
Rats -
Signal Transduction - genetics
Signal Transduction - immunology
Th1 Cells - drug effects
Th17 Cells - drug effects
Up-Regulation - drug effects
Vitamin D - pharmacology

Find related publications in this database (Keywords)
vitamin D
experimental autoimmune encephalomyelitis
multiple sclerosis
epigenetics
DNA methylation
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