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

• Published in: Journal of neuroimmunology Vol. 347; p. 577353
• Main Authors: Acar, Nazire Pinar, Tuncer, Asli, Ozkazanc, Didem, Ozbay, Feyza Gul, Karaosmanoglu, Beren, Goksen, Sibel, Sayat, Guliz, Taskiran, Ekim Z., Esendagli, Gunes, Karabudak, Rana
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.10.2020
• Subjects: Adult; Female; Fingolimod; Fingolimod Hydrochloride - pharmacology; Fingolimod Hydrochloride - therapeutic use; Humans; Immunologic Factors - pharmacology; Immunologic Factors - therapeutic use; Immunomodulation; Immunosuppressive Agents - pharmacology; Immunosuppressive Agents - therapeutic use; Interferon; Interferon-beta - pharmacology; Interferon-beta - therapeutic use; K562 Cells; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Male; Middle Aged; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - genetics; Multiple Sclerosis, Relapsing-Remitting - immunology; Next-generation sequencing; NK cells; NKp46; Transcriptome - drug effects; Transcriptome - physiology; Young Adult; Multiple sclerosis; NK cells; Next-generation sequencing; Fingolimod; Immunomodulation; Interferon; NKp46
• ISSN: 0165-5728; 1872-8421; 1872-8421
• DOI: 10.1016/j.jneuroim.2020.577353

This study aims to compare NK cells obtained from multiple sclerosis (MS) patients receiving interferon-β1 and fingolimod therapies. Fingolimod reduced the CD56bright NK cell subset. The remaining CD56dim 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 CD56dim 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. [Display omitted] •CD56dim NK cell levels are not significantly influenced in RRMS patients under prolonged IFN-β1 or fingolimod therapy•CD56dim NK cells from the patients under long-term IFN-β1 and fingolimod therapy retain functional responsiveness.•CD56dim NK cells from the patients under long-term IFN-β1 and fingolimod therapy display distinct transcriptomic signatures•Molecular signature of CD56dim cells from fingolimod-treated MS patients resemble to that of healthy individuals.