Abstract
NK/T-cell ratios predict disease activity in relapsing remitting multiple sclerosis (RRMS). We investigated in 50 RRMS patients whether interleukin-2 receptor alpha-chain (IL-2Rα) expression and shedding associates with NK/T-cell balance, as suggested by daclizumab-trials in RRMS. A subsample (N = 31) was genotyped for IL2RA-associated MS risk SNPs. CD56bright NK-cell/IL-17A+CD4+ T-cell ratios correlated negatively with plasma and PBMC-culture supernatant sIL-2Rα-levels [R = -0.209; p = 0.038 and R = -0.254; p = 0.012, resp.], and with CD4+ T-cell CD25 MFI [R = -0.341; p = 0.001]. Carriers of the rs3118470 risk-allele showed higher sIL-2Rα-levels (P = 0.031) and a lower CD56bright NK-cell/IL-17A+CD4+ T-cell ratio (P = 0.038). Therefore, IL-2Rα may be involved in the interplay between NK-cells and T-cells.
Highlights
Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system.(Dobson and Giovannoni, 2019) not fully elucidated, many factors and pathways have been suggested to be relevant for MS disease activity
We investigated the role of IL-2Rα in the interplay between natural killer (NK) and T cells in a cohort study using a homogenous group of interferon betatreated relapsing remitting multiple sclerosis (RRMS) patients
We report associations between NK/IL17A+CD4+ T cell ratios and soluble IL-2Rα (sIL-2Rα) protein shedding in vivo and in vitro, and IL-2Rα protein expression by non-regulatory CD4+ T cells
Summary
Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system.(Dobson and Giovannoni, 2019) not fully elucidated, many factors and pathways have been suggested to be relevant for MS disease activity One of these pathways is the interleukin-2 (IL-2) / interleukin-2 receptor (IL-2R) pathway.(Carrieri et al, 1992; Sorensen, 2005) IL-2 is a cytokine with both pro- and antiinflammatory effects on the immune system, well known as a survival cytokine for activated T cells, and as important in the biology of regulatory T (Treg) cells and natural killer (NK) cells.(Gaffen and Liu, 2004) The composition of the IL-2R is variable. To further consolidate our finding, we extended this analysis by exploring several other IL-2R related markers, as well as the genetic status of our participants with regard to two known IL2RA-associated MS risk alleles
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