IL2RA Methylation and Gene Expression in Relation to the Multiple Sclerosis-Associated Gene Variant rs2104286 and Soluble IL-2Rα in CD8+ T Cells

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  • Sophie Buhelt
  • Hannah Marie Laigaard
  • Marina Rode von Essen
  • Henrik Ullum
  • Annette Oturai
  • Sellebjerg, Finn Thorup
  • Helle Bach Søndergaard

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.

OriginalsprogEngelsk
Artikelnummer676141
TidsskriftFrontiers in Immunology
Vol/bind12
Antal sider10
ISSN1664-3224
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
We wish to thank laboratory technician Lisbeth Egelykke Stolpe and Ulla Abildtrup for their excellent technical assistance. We thank the Karolinska Institute in Stockholm for permission to translate and use the Genetic and Environment in Multiple Sclerosis (GEMS) questionnaire.

Publisher Copyright:
© Copyright © 2021 Buhelt, Laigaard, von Essen, Ullum, Oturai, Sellebjerg and Søndergaard.

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