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IL2RA Methylation and Gene Expression in Relation to the Multiple Sclerosis-Associated Gene Variant rs2104286 and Soluble IL-2Rα in CD8+ T Cells
by
Laigaard, Hannah-Marie
, von Essen, Marina Rode
, Sellebjerg, Finn
, Søndergaard, Helle Bach
, Ullum, Henrik
, Oturai, Annette
, Buhelt, Sophie
in
5' Untranslated regions
/ Blood & organ donations
/ CD8 antigen
/ CD8+ T cells
/ CpG islands
/ Data analysis
/ Disease
/ DNA methylation
/ Down-regulation
/ Flow cytometry
/ Gene expression
/ Genotype & phenotype
/ IL2RA
/ Immunology
/ Interleukin 2
/ Interleukin 2 receptors
/ Interleukin 7
/ interleukin-2 receptor alpha
/ Lymphocytes
/ Lymphocytes T
/ Multiple sclerosis
/ rs2104286
/ sCD25
/ Single-nucleotide polymorphism
2021
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IL2RA Methylation and Gene Expression in Relation to the Multiple Sclerosis-Associated Gene Variant rs2104286 and Soluble IL-2Rα in CD8+ T Cells
by
Laigaard, Hannah-Marie
, von Essen, Marina Rode
, Sellebjerg, Finn
, Søndergaard, Helle Bach
, Ullum, Henrik
, Oturai, Annette
, Buhelt, Sophie
in
5' Untranslated regions
/ Blood & organ donations
/ CD8 antigen
/ CD8+ T cells
/ CpG islands
/ Data analysis
/ Disease
/ DNA methylation
/ Down-regulation
/ Flow cytometry
/ Gene expression
/ Genotype & phenotype
/ IL2RA
/ Immunology
/ Interleukin 2
/ Interleukin 2 receptors
/ Interleukin 7
/ interleukin-2 receptor alpha
/ Lymphocytes
/ Lymphocytes T
/ Multiple sclerosis
/ rs2104286
/ sCD25
/ Single-nucleotide polymorphism
2021
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IL2RA Methylation and Gene Expression in Relation to the Multiple Sclerosis-Associated Gene Variant rs2104286 and Soluble IL-2Rα in CD8+ T Cells
by
Laigaard, Hannah-Marie
, von Essen, Marina Rode
, Sellebjerg, Finn
, Søndergaard, Helle Bach
, Ullum, Henrik
, Oturai, Annette
, Buhelt, Sophie
in
5' Untranslated regions
/ Blood & organ donations
/ CD8 antigen
/ CD8+ T cells
/ CpG islands
/ Data analysis
/ Disease
/ DNA methylation
/ Down-regulation
/ Flow cytometry
/ Gene expression
/ Genotype & phenotype
/ IL2RA
/ Immunology
/ Interleukin 2
/ Interleukin 2 receptors
/ Interleukin 7
/ interleukin-2 receptor alpha
/ Lymphocytes
/ Lymphocytes T
/ Multiple sclerosis
/ rs2104286
/ sCD25
/ Single-nucleotide polymorphism
2021
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IL2RA Methylation and Gene Expression in Relation to the Multiple Sclerosis-Associated Gene Variant rs2104286 and Soluble IL-2Rα in CD8+ T Cells
Journal Article
IL2RA Methylation and Gene Expression in Relation to the Multiple Sclerosis-Associated Gene Variant rs2104286 and Soluble IL-2Rα in CD8+ T Cells
2021
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Overview
CD8 + T cells are involved in the pathogenesis of multiple sclerosis (MS). The interleukin-2 receptor α (IL-2Rα) is important for CD8 + T cell function, and single nucleotide polymorphisms (SNPs) in the IL2RA gene encoding IL-2Rα increase the risk of MS. Therefore, in isolated CD8 + T cells we investigated IL2RA gene methylation and gene expression in relation to the MS-associated IL2RA SNP rs2104286 and soluble IL-2Rα (sIL-2Rα). We have identified allele specific methylation of the CpG-site located in intron 1 that is perturbed by the rs2104286 SNP in CD8 + T cells from genotype-selected healthy subjects (HS). However, methylation of selected CpG-sites in the promotor or 5’UTR region of the IL2RA gene was neither associated with the rs2104286 SNP nor significantly correlated with IL2RA gene expression in HS. In CD8 + T cells from HS, we explored expression of immune relevant genes but observed only few associations with the rs2104286 SNP. However, we found that sIL-2Rα correlated negatively with expression of 55 immune relevant genes, including the IL-7 receptor gene, with Spearman’s rho between -0.49 and -0.32. Additionally, in HS by use of flow cytometry we observed that the IL-7 receptor on naïve CD8 + T cells correlated negatively with sIL-2Rα and was downregulated in carriers of the rs2104286 MS-associated risk genotype. Collectively, our study of resting CD8 + T cells indicates that the rs2104286 SNP has a minor effect and sIL-2Rα may negatively regulate the CD8 + T cell response.
Publisher
Frontiers Media SA,Frontiers Media S.A
Subject
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