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IL7RA haplotype-associated alterations in cellular immune function and gene expression patterns in multiple sclerosis

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IL7RA haplotype-associated alterations in cellular immune function and gene expression patterns in multiple sclerosis. / Jäger, J; Schulze, C; Rösner, S; Martin, R.

In: GENES IMMUN, Vol. 14, No. 7, 01.10.2013, p. 453-61.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Jäger, J, Schulze, C, Rösner, S & Martin, R 2013, 'IL7RA haplotype-associated alterations in cellular immune function and gene expression patterns in multiple sclerosis', GENES IMMUN, vol. 14, no. 7, pp. 453-61. https://doi.org/10.1038/gene.2013.40

APA

Jäger, J., Schulze, C., Rösner, S., & Martin, R. (2013). IL7RA haplotype-associated alterations in cellular immune function and gene expression patterns in multiple sclerosis. GENES IMMUN, 14(7), 453-61. https://doi.org/10.1038/gene.2013.40

Vancouver

Jäger J, Schulze C, Rösner S, Martin R. IL7RA haplotype-associated alterations in cellular immune function and gene expression patterns in multiple sclerosis. GENES IMMUN. 2013 Oct 1;14(7):453-61. https://doi.org/10.1038/gene.2013.40

Bibtex

@article{0185d344ae154555a74b83e6f1d3e2b1,
title = "IL7RA haplotype-associated alterations in cellular immune function and gene expression patterns in multiple sclerosis",
abstract = "Interleukin-7 receptor alpha (IL7RA) is among the top listed candidate genes influencing the risk to develop multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. Soluble IL-7RA (sIL-7RA) protein and mRNA levels vary among the four common IL7RA haplotypes. Here we show and confirm that protective haplotype carriers have three times lower sIL-7RA serum levels than the other three haplotypes. High sIL-7RA concentrations significantly decrease IL-7-mediated STAT5 phosphorylation in CD4(+) T cells. Transcriptome analysis of unstimulated and stimulated CD4(+) T cells of MS patients carrying the different IL7RA haplotypes revealed complex and overlapping patterns in genes participating in cytokine signaling networks, apoptosis, cell cycle progression and cell differentiation. Our findings indicate that genetic variants of IL7RA result in haplotype-associated differential responsiveness to immunological stimuli that influence MS susceptibility not exclusively by varying levels of sIL-7RA.",
keywords = "Adult, CD4-Positive T-Lymphocytes, Female, Gene Regulatory Networks, Haplotypes, Humans, Interleukin-7 Receptor alpha Subunit, Killer Cells, Natural, Male, Middle Aged, Multiple Sclerosis, Phosphorylation, Polymorphism, Single Nucleotide, STAT5 Transcription Factor, Transcription, Genetic",
author = "J J{\"a}ger and C Schulze and S R{\"o}sner and R Martin",
year = "2013",
month = oct,
day = "1",
doi = "10.1038/gene.2013.40",
language = "English",
volume = "14",
pages = "453--61",
journal = "GENES IMMUN",
issn = "1466-4879",
publisher = "NATURE PUBLISHING GROUP",
number = "7",

}

RIS

TY - JOUR

T1 - IL7RA haplotype-associated alterations in cellular immune function and gene expression patterns in multiple sclerosis

AU - Jäger, J

AU - Schulze, C

AU - Rösner, S

AU - Martin, R

PY - 2013/10/1

Y1 - 2013/10/1

N2 - Interleukin-7 receptor alpha (IL7RA) is among the top listed candidate genes influencing the risk to develop multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. Soluble IL-7RA (sIL-7RA) protein and mRNA levels vary among the four common IL7RA haplotypes. Here we show and confirm that protective haplotype carriers have three times lower sIL-7RA serum levels than the other three haplotypes. High sIL-7RA concentrations significantly decrease IL-7-mediated STAT5 phosphorylation in CD4(+) T cells. Transcriptome analysis of unstimulated and stimulated CD4(+) T cells of MS patients carrying the different IL7RA haplotypes revealed complex and overlapping patterns in genes participating in cytokine signaling networks, apoptosis, cell cycle progression and cell differentiation. Our findings indicate that genetic variants of IL7RA result in haplotype-associated differential responsiveness to immunological stimuli that influence MS susceptibility not exclusively by varying levels of sIL-7RA.

AB - Interleukin-7 receptor alpha (IL7RA) is among the top listed candidate genes influencing the risk to develop multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. Soluble IL-7RA (sIL-7RA) protein and mRNA levels vary among the four common IL7RA haplotypes. Here we show and confirm that protective haplotype carriers have three times lower sIL-7RA serum levels than the other three haplotypes. High sIL-7RA concentrations significantly decrease IL-7-mediated STAT5 phosphorylation in CD4(+) T cells. Transcriptome analysis of unstimulated and stimulated CD4(+) T cells of MS patients carrying the different IL7RA haplotypes revealed complex and overlapping patterns in genes participating in cytokine signaling networks, apoptosis, cell cycle progression and cell differentiation. Our findings indicate that genetic variants of IL7RA result in haplotype-associated differential responsiveness to immunological stimuli that influence MS susceptibility not exclusively by varying levels of sIL-7RA.

KW - Adult

KW - CD4-Positive T-Lymphocytes

KW - Female

KW - Gene Regulatory Networks

KW - Haplotypes

KW - Humans

KW - Interleukin-7 Receptor alpha Subunit

KW - Killer Cells, Natural

KW - Male

KW - Middle Aged

KW - Multiple Sclerosis

KW - Phosphorylation

KW - Polymorphism, Single Nucleotide

KW - STAT5 Transcription Factor

KW - Transcription, Genetic

U2 - 10.1038/gene.2013.40

DO - 10.1038/gene.2013.40

M3 - SCORING: Journal article

C2 - 23985573

VL - 14

SP - 453

EP - 461

JO - GENES IMMUN

JF - GENES IMMUN

SN - 1466-4879

IS - 7

ER -