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Genomic Effects of the Vitamin D Receptor: Potentially the Link between Vitamin D, Immune Cells, and Multiple Sclerosis.
Front Immunol 2018; 9:477FI

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.

Authors+Show Affiliations

Menzies Institute for Medical Research Tasmania, Hobart, TAS, Australia.Menzies Institute for Medical Research Tasmania, Hobart, TAS, Australia.Menzies Institute for Medical Research Tasmania, Hobart, TAS, Australia. Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Engineering Technology Research Center of Anti-inflammatory and Immunodrugs in Anhui Province, Hefei, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

29593729

Citation

Lu, Ming, et al. "Genomic Effects of the Vitamin D Receptor: Potentially the Link Between Vitamin D, Immune Cells, and Multiple Sclerosis." Frontiers in Immunology, vol. 9, 2018, p. 477.
Lu M, Taylor BV, Körner H. Genomic Effects of the Vitamin D Receptor: Potentially the Link between Vitamin D, Immune Cells, and Multiple Sclerosis. Front Immunol. 2018;9:477.
Lu, M., Taylor, B. V., & Körner, H. (2018). Genomic Effects of the Vitamin D Receptor: Potentially the Link between Vitamin D, Immune Cells, and Multiple Sclerosis. Frontiers in Immunology, 9, p. 477. doi:10.3389/fimmu.2018.00477.
Lu M, Taylor BV, Körner H. Genomic Effects of the Vitamin D Receptor: Potentially the Link Between Vitamin D, Immune Cells, and Multiple Sclerosis. Front Immunol. 2018;9:477. PubMed PMID: 29593729.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genomic Effects of the Vitamin D Receptor: Potentially the Link between Vitamin D, Immune Cells, and Multiple Sclerosis. AU - Lu,Ming, AU - Taylor,Bruce V, AU - Körner,Heinrich, Y1 - 2018/03/12/ PY - 2017/11/22/received PY - 2018/02/22/accepted PY - 2018/3/30/entrez PY - 2018/3/30/pubmed PY - 2018/3/30/medline KW - environment KW - genetics KW - immune system KW - multiple sclerosis KW - vitamin D SP - 477 EP - 477 JF - Frontiers in immunology JO - Front Immunol VL - 9 N2 - 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. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/29593729/Genomic_Effects_of_the_Vitamin_D_Receptor:_Potentially_the_Link_between_Vitamin_D_Immune_Cells_and_Multiple_Sclerosis_ L2 - https://dx.doi.org/10.3389/fimmu.2018.00477 DB - PRIME DP - Unbound Medicine ER -