An immunological and transcriptomics approach on differential modulation of NK cells in multiple sclerosis patients under interferon-β1 and fingolimod therapy

Nazire Pinar Acar; Asli Tuncer; Didem Ozkazanc; Feyza Gul Ozbay; Beren Karaosmanoglu; Sibel Goksen; Guliz Sayat; Ekim Z Taskiran; Gunes Esendagli; Rana Karabudak

doi:10.1016/j.jneuroim.2020.577353

An immunological and transcriptomics approach on differential modulation of NK cells in multiple sclerosis patients under interferon-β1 and fingolimod therapy

J Neuroimmunol. 2020 Oct 15:347:577353. doi: 10.1016/j.jneuroim.2020.577353. Epub 2020 Jul 30.

Authors

Affiliations

¹ Department of Neurology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
² Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.
³ Department of Medical Genetics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
⁴ Department of Medical and Surgical Research, Institute of Health Sciences, Hacettepe University, Ankara, Turkey.
⁵ Department of Medical Genetics, Faculty of Medicine, Hacettepe University, Ankara, Turkey; Department of Medical and Surgical Research, Institute of Health Sciences, Hacettepe University, Ankara, Turkey.
⁶ Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey; Department of Medical and Surgical Research, Institute of Health Sciences, Hacettepe University, Ankara, Turkey. Electronic address: gunese@hacettepe.edu.tr.

PMID: 32745802
DOI: 10.1016/j.jneuroim.2020.577353

Abstract

This study aims to compare NK cells obtained from multiple sclerosis (MS) patients receiving interferon-β1 and fingolimod therapies. Fingolimod reduced the CD56^bright NK cell subset. The remaining CD56^dim NK cells displayed NKG2D, NKp46, CD107a, and IFN-γ levels similar to those from the patients under interferon-β1 therapy. Alternatively, comparative transcriptomics and pathway analyses revealed significant distinctions between two therapy modalities. Molecular signature of the CD56^dim NK cells from fingolimod-treated MS patients was closely associated to those from healthy subjects. The basic assets of NK cells were modestly influenced by interferon-β1 and fingolimod, however transcriptomics showed profound alterations in NK responses.

Keywords: Fingolimod; Immunomodulation; Interferon; Multiple sclerosis; NK cells; NKp46; Next-generation sequencing.

MeSH terms

Adult
Female
Fingolimod Hydrochloride / pharmacology
Fingolimod Hydrochloride / therapeutic use*
Humans
Immunologic Factors / pharmacology
Immunologic Factors / therapeutic use
Immunosuppressive Agents / pharmacology
Immunosuppressive Agents / therapeutic use
Interferon-beta / pharmacology
Interferon-beta / therapeutic use*
K562 Cells
Killer Cells, Natural / drug effects
Killer Cells, Natural / immunology*
Male
Middle Aged
Multiple Sclerosis, Relapsing-Remitting / drug therapy*
Multiple Sclerosis, Relapsing-Remitting / genetics
Multiple Sclerosis, Relapsing-Remitting / immunology*
Transcriptome / drug effects
Transcriptome / physiology*
Young Adult

Substances

Immunologic Factors
Immunosuppressive Agents
Interferon-beta
Fingolimod Hydrochloride