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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	118-127
Number of pages	10
Journal	Genes and Immunity
Volume	17
Issue number	2
DOIs	https://doi.org/10.1038/gene.2015.61
Publication status	Published - Mar 2016
Externally published	Yes

Bibliographical note

Funding Information:
TB has received an unrestricted grant for running expenses in this project from Biogen Idec Norway AS, ISL has received unrestricted grant for salary expenses from Novartis Norway AS and TH has received research grants from Merck Serono.

Publisher Copyright:
© 2016 Macmillan Publishers Limited.

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The multiple sclerosis susceptibility genes TAGAP and IL2RA are regulated by vitamin D in CD4+ T cellsFinal published version, 1.28 MBLicence: CC BY-NC-ND

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Berge, T., Leikfoss, I. S., Brorson, I. S., Bos, S. D., Page, C. M., Gustavsen, M. W., Bjølgerud, A., Holmøy, T., Celius, E. G., Damoiseaux, J., Smolders, J., Harbo, H. F., & Spurkland, A. (2016). The multiple sclerosis susceptibility genes TAGAP and IL2RA are regulated by Vitamin D in CD4+ T cells. Genes and Immunity, 17(2), 118-127. https://doi.org/10.1038/gene.2015.61

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title = "The multiple sclerosis susceptibility genes TAGAP and IL2RA are regulated by Vitamin D in CD4+ T cells",

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.",

author = "T. Berge and Leikfoss, {I. S.} and Brorson, {I. S.} and Bos, {S. D.} and Page, {C. M.} and Gustavsen, {M. W.} and A. Bj{\o}lgerud and T. Holm{\o}y and Celius, {E. G.} and J. Damoiseaux and J. Smolders and Harbo, {H. F.} and A. Spurkland",

note = "Funding Information: TB has received an unrestricted grant for running expenses in this project from Biogen Idec Norway AS, ISL has received unrestricted grant for salary expenses from Novartis Norway AS and TH has received research grants from Merck Serono. Publisher Copyright: {\textcopyright} 2016 Macmillan Publishers Limited.",

year = "2016",

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doi = "10.1038/gene.2015.61",

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AU - Berge, T.

AU - Leikfoss, I. S.

AU - Brorson, I. S.

AU - Bos, S. D.

AU - Page, C. M.

AU - Gustavsen, M. W.

AU - Bjølgerud, A.

AU - Holmøy, T.

AU - Celius, E. G.

AU - Damoiseaux, J.

AU - Smolders, J.

AU - Harbo, H. F.

AU - Spurkland, A.

N1 - Funding Information: TB has received an unrestricted grant for running expenses in this project from Biogen Idec Norway AS, ISL has received unrestricted grant for salary expenses from Novartis Norway AS and TH has received research grants from Merck Serono. Publisher Copyright: © 2016 Macmillan Publishers Limited.

PY - 2016/3

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N2 - 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.

AB - 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.

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

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