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Cells. 2019 Jun 25;8(6). pii: E634. doi: 10.3390/cells8060634.

Relationship between Multiple Sclerosis-Associated IL2RA Risk Allele Variants and Circulating T Cell Phenotypes in Healthy Genotype-Selected Controls.

Author information

1
Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, 2600 Glostrup, Denmark. sophie.buhelt.01@regionh.dk.
2
Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, 2600 Glostrup, Denmark. hbs@rh.dk.
3
Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, 2600 Glostrup, Denmark. abo@rh.dk.
4
Department of Clinical Immunology, Center of Clinical Investigation, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark. Henrik.Ullum@regionh.dk.
5
Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, 2600 Glostrup, Denmark. marina.rode.von.essen@regionh.dk.
6
Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, 2600 Glostrup, Denmark. finn.thorup.sellebjerg@regionh.dk.

Abstract

Single nucleotide polymorphisms (SNPs) in or near the IL2RA gene, that encodes the interleukin-2 (IL-2) receptor α (CD25), are associated with increased risk of immune-mediated diseases including multiple sclerosis (MS). We investigated how the MS-associated IL2RA SNPs rs2104286 and rs11256593 are associated with CD25 expression on T cells ex vivo by multiparameter flow cytometry in paired genotype-selected healthy controls. We observed that MS-associated IL2RA SNPs rs2104286 and rs11256593 are associated with expression of CD25 in CD4+ but not CD8+ T cells. In CD4+ T cells, carriers of the risk genotype had a reduced frequency of CD25+ TFH1 cells (p = 0.001) and an increased frequency of CD25+ recent thymic emigrant cells (p = 0.006). Furthermore, carriers of the risk genotype had a reduced surface expression of CD25 in post-thymic expanded CD4+ T cells (CD31-CD45RA+), CD39+ TReg cells and in several non-follicular memory subsets. Our study found novel associations of MS-associated IL2RA SNPs on expression of CD25 in CD4+ T cell subsets. Insight into the associations of MS-associated IL2RA SNPs, as these new findings provide, offers a better understanding of CD25 variation in the immune system and can lead to new insights into how MS-associated SNPs contribute to development of MS.

KEYWORDS:

CD25; IL2RA; interleukin-2 receptor; multiple sclerosis; rs11256593; rs2104286

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