IL2RA Methylation and Gene Expression in Relation to the Multiple Sclerosis-Associated Gene Variant rs2104286 and Soluble IL-2Rα in CD8+ T Cells
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 investig...
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doaj-52d1f68b9f9c4755afc99eeeef97ab3c2021-07-27T09:08:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-07-011210.3389/fimmu.2021.676141676141IL2RA Methylation and Gene Expression in Relation to the Multiple Sclerosis-Associated Gene Variant rs2104286 and Soluble IL-2Rα in CD8+ T CellsSophie Buhelt0Hannah-Marie Laigaard1Marina Rode von Essen2Henrik Ullum3Annette Oturai4Finn Sellebjerg5Finn Sellebjerg6Helle Bach Søndergaard7Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Glostrup, DenmarkDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Glostrup, DenmarkDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Glostrup, DenmarkStatens Serum Institut, Copenhagen, DenmarkDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Glostrup, DenmarkDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Glostrup, DenmarkDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, DenmarkDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Glostrup, DenmarkCD8+ 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.676141/fullmultiple sclerosisCD8+ T cellsinterleukin-2 receptor alphasCD25IL2RArs2104286 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sophie Buhelt Hannah-Marie Laigaard Marina Rode von Essen Henrik Ullum Annette Oturai Finn Sellebjerg Finn Sellebjerg Helle Bach Søndergaard |
spellingShingle |
Sophie Buhelt Hannah-Marie Laigaard Marina Rode von Essen Henrik Ullum Annette Oturai Finn Sellebjerg Finn Sellebjerg Helle Bach Søndergaard IL2RA Methylation and Gene Expression in Relation to the Multiple Sclerosis-Associated Gene Variant rs2104286 and Soluble IL-2Rα in CD8+ T Cells Frontiers in Immunology multiple sclerosis CD8+ T cells interleukin-2 receptor alpha sCD25 IL2RA rs2104286 |
author_facet |
Sophie Buhelt Hannah-Marie Laigaard Marina Rode von Essen Henrik Ullum Annette Oturai Finn Sellebjerg Finn Sellebjerg Helle Bach Søndergaard |
author_sort |
Sophie Buhelt |
title |
IL2RA Methylation and Gene Expression in Relation to the Multiple Sclerosis-Associated Gene Variant rs2104286 and Soluble IL-2Rα in CD8+ T Cells |
title_short |
IL2RA Methylation and Gene Expression in Relation to the Multiple Sclerosis-Associated Gene Variant rs2104286 and Soluble IL-2Rα in CD8+ T Cells |
title_full |
IL2RA Methylation and Gene Expression in Relation to the Multiple Sclerosis-Associated Gene Variant rs2104286 and Soluble IL-2Rα in CD8+ T Cells |
title_fullStr |
IL2RA Methylation and Gene Expression in Relation to the Multiple Sclerosis-Associated Gene Variant rs2104286 and Soluble IL-2Rα in CD8+ T Cells |
title_full_unstemmed |
IL2RA Methylation and Gene Expression in Relation to the Multiple Sclerosis-Associated Gene Variant rs2104286 and Soluble IL-2Rα in CD8+ T Cells |
title_sort |
il2ra methylation and gene expression in relation to the multiple sclerosis-associated gene variant rs2104286 and soluble il-2rα in cd8+ t cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-07-01 |
description |
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. |
topic |
multiple sclerosis CD8+ T cells interleukin-2 receptor alpha sCD25 IL2RA rs2104286 |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.676141/full |
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