The multiple sclerosis susceptibility genes TAGAP and IL2RA are regulated by vitamin D in CD4+ T cells

T Berge; I S Leikfoss; I S Brorson; S D Bos; C M Page; M W Gustavsen; A Bjølgerud; T Holmøy; E G Celius; J Damoiseaux; J Smolders; H F Harbo; A Spurkland

doi:10.1038/gene.2015.61

The multiple sclerosis susceptibility genes TAGAP and IL2RA are regulated by vitamin D in CD4+ T cells

Genes Immun. 2016 Mar;17(2):118-27. doi: 10.1038/gene.2015.61. Epub 2016 Jan 14.

Authors

T Berge¹, I S Leikfoss^{1

2}, I S Brorson^{1

2}, S D Bos^{1

2}, C M Page^{1

2}, M W Gustavsen^{1

2}, A Bjølgerud^{1

2}, T Holmøy^{2

3}, E G Celius¹, J Damoiseaux⁴, J Smolders⁵, H F Harbo^{1

2}, A Spurkland⁶

Affiliations

¹ Department of Neurology, Oslo University Hospital, Oslo, Norway.
² Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³ Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
⁴ Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands.
⁵ Department of Neurology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
⁶ Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

Abstract

Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system that develops in genetically susceptible individuals. The majority of the MS-associated gene variants are located in genetic regions with importance for T-cell differentiation. Vitamin D is a potent immunomodulator, and vitamin D deficiency has been suggested to be associated with increased MS disease susceptibility and activity. In CD4+ T cells, we have analyzed in vitro vitamin D responsiveness of genes that contain an MS-associated single-nucleotide polymorphism (SNP) and with one or more vitamin D response elements in their regulatory regions. We identify IL2RA and TAGAP as novel vitamin D target genes. The vitamin D response is observed in samples from both MS patients and controls, and is not dependent on the genotype of MS-associated SNPs in the respective genes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
CD4-Positive T-Lymphocytes / drug effects*
CD4-Positive T-Lymphocytes / metabolism
CD4-Positive T-Lymphocytes / pathology
Female
GTPase-Activating Proteins / agonists
GTPase-Activating Proteins / blood
GTPase-Activating Proteins / genetics*
Gene Expression
Gene Expression Profiling
Genetic Predisposition to Disease
Humans
Interleukin-2 Receptor alpha Subunit / antagonists & inhibitors
Interleukin-2 Receptor alpha Subunit / blood
Interleukin-2 Receptor alpha Subunit / genetics*
Male
Middle Aged
Multiple Sclerosis / blood
Multiple Sclerosis / genetics*
Multiple Sclerosis / pathology
Polymorphism, Single Nucleotide
Primary Cell Culture
Receptors, Calcitriol / blood
Receptors, Calcitriol / genetics*
Response Elements
Vitamin D / blood
Vitamin D / pharmacology*

Substances

GTPase-Activating Proteins
IL2RA protein, human
Interleukin-2 Receptor alpha Subunit
Receptors, Calcitriol
TAGAP protein, human
VDR protein, human
Vitamin D