A Single Nucleotide Polymorphism within the Interleukin-7 Receptor Alpha Promoter Influences Recent Thymic Emigrants in Multiple Sclerosis

Abstract

Recently, several new multiple sclerosis (MS) risk genes, including the interleukin-7 receptor α chain (IL-7Rα, CD127), have been identified by genome wide association studies. Since IL-7R triggering plays an important role in T cell development and survival, we postulate that polymorphisms within the IL-7Rα gene could affect T cell function in patients with MS. Therefore, we correlated the genotypes of MS patients (n=65) and healthy controls(HC, n=33) with frequencies of regulatory T cells (Treg) and expression of CD31 and CD127 in both Treg and Conventional T cells (Tconv). CD31 is a marker for recent thymic emigrants (RTE), which are characterized by high T cell receptor excision circles (TREC) and a low number of cell divisions. We found that the MS associated SNP rs6897932 does not influence the frequency of CD4+ CD25hi CD127low Tregs, nor the frequency of CD31+ T cells or expression levels of CD127 for both Tconv and Tregs. Another SNP (rs11567685; C/T) within the IL-7Rα promoter region was reported to influence the expression of CD127 on T cells of primary progressive MS patients. We found that there was a trend towards higher expression of CD127 on Tconv (p = 0.14), but not on Tregs of MS patients carrying the C allele. Strikingly, the frequency of CD31+ naïve (CD45RA+) Tconv and Tregs was significantly reduced in MS patients that are homozygous for the T allele (Tconv, p = 0.001; Tregs, p = 0.005). These results point towards a contribution of this promoter SNP to alterations in T cell development reported in MS patients.