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Fingolimod therapy in multiple sclerosis leads to the enrichment of a subpopulation of aged NK cells

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Item Type:Article
Title:Fingolimod therapy in multiple sclerosis leads to the enrichment of a subpopulation of aged NK cells
Creators Name:Schwichtenberg, S.C. and Wisgalla, A. and Schroeder-Castagno, M. and Alvarez-González, C. and Schlickeiser, S. and Siebert, N. and Bellmann-Strobl, J. and Wernecke, K.D. and Paul, F. and Dörr, J. and Infante-Duarte, C.
Abstract:Fingolimod is an approved oral treatment for relapsing–remitting multiple sclerosis (RRMS) that modulates agonistically the sphingosin-1-phosphate receptor (S1PR), inhibiting thereby the egress of lymphocytes from the lymph nodes. In this interventional prospective clinical phase IV trial, we longitudinally investigated the impact of fingolimod on frequencies of NK cell subpopulations by flow cytometry in 17 RRMS patients at baseline and 1, 3, 6, and 12 months after treatment initiation. Clinical outcome was assessed by the Expanded Disability Status Scale (EDSS) and annualized relapse rates (ARR). Over the study period, median EDSS remained stable from month 3 to month 12, and ARR decreased compared to ARR in the 24 months prior treatment. Treatment was paralleled by an increased frequency of circulating NK cells, due primarily to an increase in CD56(dim)CD94(low) mature NK cells, while the CD56(bright) fraction and CD127(+) innate lymphoid cells (ILCs) decreased over time. An unsupervised clustering algorithm further revealed that a particular fraction of NK cells defined by the expression of CD56(dim)CD16(++)KIR(+/-)NKG2A(-)CD94(-)CCR7(+/-)CX(3)CR1(+/-)NKG2C(-)NKG2D(+)NKp46(-)DNAM1(++)CD127(+) increased during treatment. This specific phenotype might reflect a status of aged, fully differentiated, and less functional NK cells. Our study confirms that fingolimod treatment affects both NK cells and ILC. In addition, our study suggests that treatment leads to the enrichment of a specific NK cell subset characterized by an aged phenotype. This might limit the anti-microbial and anti-tumour NK cell activity in fingolimod-treated patients.
Keywords:Natural Killer (NK) Cells, Fingolimod, Multiple Sclerosis (MS), Innate Lymphoid Cells (ILCs), Sphingosin-1-Phosphate Receptor (S1PR)
Page Range:1783-1797
Date:July 2021
Official Publication:https://doi.org/10.1007/s13311-021-01078-7
PubMed:View item in PubMed

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