TY - JOUR

T1 - Relationship between Multiple Sclerosis-Associated IL2RA Risk Allele Variants and Circulating T Cell Phenotypes in Healthy Genotype-Selected Controls

AU - Buhelt, Sophie

AU - Søndergaard, Helle Bach

AU - Oturai, Annette

AU - Ullum, Henrik

AU - von Essen, Marina Rode

AU - Sellebjerg, Finn

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Alleles

KW - Antigens, CD/metabolism

KW - CD4-Positive T-Lymphocytes/immunology

KW - CD8-Positive T-Lymphocytes/immunology

KW - Case-Control Studies

KW - Female

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Genotype

KW - Humans

KW - Immunologic Memory

KW - Interleukin-2 Receptor alpha Subunit/genetics

KW - Male

KW - Middle Aged

KW - Multiple Sclerosis/genetics

KW - Phenotype

KW - Risk Factors

KW - T-Lymphocytes/immunology

KW - Young Adult

U2 - 10.3390/cells8060634

DO - 10.3390/cells8060634

M3 - Journal article

C2 - 31242590

VL - 8

JO - Cells

JF - Cells

SN - 2073-4409

IS - 6

M1 - 634

ER -