NK/T cell ratios associate with interleukin-2 receptor alpha chain expression and shedding in multiple sclerosis

M Mimpen; L Rolf; AH Muris; O Gerlach; G Poelmans; R Hupperts; Joost Smolders; J Damoiseaux

doi:10.1016/j.jneuroim.2021.577499

NK/T cell ratios associate with interleukin-2 receptor alpha chain expression and shedding in multiple sclerosis

M Mimpen, L Rolf, AH Muris, O Gerlach, G Poelmans, R Hupperts, Joost Smolders, J Damoiseaux

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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. CD56^bright 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 CD56^bright 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.

Original language	English
Article number	577499
Journal	Journal of Neuroimmunology
Volume	353
DOIs	https://doi.org/10.1016/j.jneuroim.2021.577499
Publication status	Published - 15 Apr 2021

Bibliographical note

Funding Information:
We would like to thank Daphne Peerlings for exploring the IL-2Rα data. This study was funded by Nationaal MS Fonds grant OZ2016-001 and an unrestricted grant by Merck.

Publisher Copyright:
© 2021 The Author(s)

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title = "NK/T cell ratios associate with interleukin-2 receptor alpha chain expression and shedding in multiple sclerosis",

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.",

author = "M Mimpen and L Rolf and AH Muris and O Gerlach and G Poelmans and R Hupperts and Joost Smolders and J Damoiseaux",

note = "Funding Information: We would like to thank Daphne Peerlings for exploring the IL-2Rα data. This study was funded by Nationaal MS Fonds grant OZ2016-001 and an unrestricted grant by Merck. Publisher Copyright: {\textcopyright} 2021 The Author(s)",

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T1 - NK/T cell ratios associate with interleukin-2 receptor alpha chain expression and shedding in multiple sclerosis

AU - Mimpen, M

AU - Rolf, L

AU - Muris, AH

AU - Gerlach, O

AU - Poelmans, G

AU - Hupperts, R

AU - Smolders, Joost

AU - Damoiseaux, J

N1 - Funding Information: We would like to thank Daphne Peerlings for exploring the IL-2Rα data. This study was funded by Nationaal MS Fonds grant OZ2016-001 and an unrestricted grant by Merck. Publisher Copyright: © 2021 The Author(s)

PY - 2021/4/15

Y1 - 2021/4/15

N2 - 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.

AB - 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.

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DO - 10.1016/j.jneuroim.2021.577499

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NK/T cell ratios associate with interleukin-2 receptor alpha chain expression and shedding in multiple sclerosis

Abstract

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