Abstract
Vitamin D has a plethora of functions that are important for the maintenance of general health and in particular, the functional integrity of the immune system, such as promoting an anti-inflammatory cytokine profile and reducing the Treg/Th17 ratio. Multiple sclerosis (MS) is a chronic, inflammatory, and neurodegenerative central nervous system (CNS) disorder of probable autoimmune origin. MS is characterized by recurring or progressive demyelination and degeneration of the CNS due in part to a misguided immune response to as yet undefined (CNS) antigens, potentially including myelin basic protein and proteolipid protein. MS has also been shown to be associated significantly with environmental factors such as the lack of vitamin D. The role of vitamin D in the pathogenesis and progression of MS is complex. Recent genetic studies have shown that various common MS-associated risk-single-nucleotide polymorphisms (SNPs) are located within or in the vicinity of genes associated with the complex metabolism of vitamin D. The functional aspects of these genetic associations may be explained either by a direct SNP-associated loss- or gain-of-function in a vitamin D-associated gene or due to a change in the regulation of gene expression in certain immune cell types. The development of new genetic tools using next-generation sequencing: e.g., chromatin immunoprecipitation sequencing (ChIP-seq) and the accompanying rapid progress of epigenomics has made it possible to recognize that the association between vitamin D and MS could be based on the extensive and characteristic genomic binding of the vitamin D receptor (VDR). Therefore, it is important to analyze comprehensively the spatiotemporal VDR binding patterns that have been identified using ChIP-seq in multiple immune cell types to reveal an integral profile of genomic VDR interaction. In summary, the aim of this review is to connect genomic effects vitamin D has on immune cells with MS and thus, to contribute to a better understanding of the influence of vitamin D on the etiology and the pathogenesis of this complex autoimmune disease.
Highlights
Vitamin D was named as the fourth factor identified in an experimental rickets model [1]
The association of the vitamin D receptor (VDR) cistrome with epigenomic characteristics, including SE regions, in these cells, could help to analyze the potential mechanisms underlying the role of vitamin D in Multiple sclerosis (MS) etiology and pathogenesis
Recent immune cell plasticity research emphasized the importance of transcription factor (TF) that are dependent on environmental signals, such as VDR, SMAD3 (TGF-β-dependent), and STAT, which participate in the modification of enhancer landscapes and interact with master TFs, such as T-BET, PU.1 and OCT4
Summary
Vitamin D was named as the fourth factor identified in an experimental rickets model [1]. A second major aspect of the role of vitamin D in the etiology of MS are the extensive genomic binding regions of the nuclear vitamin D receptor (VDR), which is the only cognate receptor of the active form of vitamin D [1,25(OH)2D3 or calcitriol]. It acts as a transcription factor (TF) that interacts with multiple other TFs and coregulators, and binds to regulatory hotspots throughout the genome [29, 30]. The association of the VDR cistrome with epigenomic characteristics, including SE regions, in these cells, could help to analyze the potential mechanisms underlying the role of vitamin D in MS etiology and pathogenesis
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