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

Acar, Nazire Pınar; Tuncer, Aslı; Özkazanç, Didem; Özbay, Feyza Gül; Karaosmanoğlu, Beren; Goksen, Sibel; Sayat, Guliz; Taşkıran, Ekim Z.; Esendağlı, Güneş; Karabudak, Rana

doi:10.1016/j.jneuroim.2020.577353

Cited by 7 publications

(10 citation statements)

References 36 publications

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“…An increased frequency of circulating CD56 dim mature NK cells was found while the frequency of CD56 bright and CD127 + ILCs decreased over time (58). This is in line with two other studies reporting a significant decrease of CD56 bright NK cells in the peripheral blood of FYT20 treated patients (55,57). Other studies found that in FYT20 treated MS patients the percentage of NK cells increased when compared to treatment-naïve patients (56) or that NK cells were not affected by FYT20 (59).…”

Section: Role Of Ilcs In Ms: Lessons Learned From Dmtssupporting

confidence: 90%

“…Studies show that MS patients treated with DMF have reduced percentages of pro-inflammatory CD4 + and CD8 + T cells and an expansion of CD56 bright NK cells and a modest increase in absolute numbers of CD56 dim cells (55,56). FYT20, a sphingosine 1-phosphate receptor agonist used as an oral compound for the treatment of MS shows efficacy in reducing inflammation in the CNS of MS patients (57). NK cells express two receptors affected by this treatment-S1PR1 and S1PR5 consequently affecting their egress from the lymph nodes (3).…”

Section: Role Of Ilcs In Ms: Lessons Learned From Dmtsmentioning

confidence: 99%

“…NK cells express two receptors affected by this treatment-S1PR1 and S1PR5 consequently affecting their egress from the lymph nodes (3). Data on the effect of long-term FTY20 treatment on NK cells are however contradictory (57,59,64). In a clinical phase IV trial in 17 RRMS patients, the longitude impact of FYT20 treatment on NK cells was assessed (58).…”

Section: Role Of Ilcs In Ms: Lessons Learned From Dmtsmentioning

confidence: 99%

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Innate Lymphoid Cells - Neglected Players in Multiple Sclerosis

et al. 2022

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Multiple sclerosis (MS) is a highly debilitating autoimmune disease affecting millions of individuals worldwide. Although classically viewed as T-cell mediated disease, the role of innate lymphoid cells (ILC) such as natural killer (NK) cells and ILC 1-3s has become a focal point as several findings implicate them in the disease pathology. The role of ILCs in MS is still not completely understood as controversial findings have been reported assigning them either a protective or disease-accelerating role. Recent findings in experimental autoimmune encephalomyelitis (EAE) suggest that ILCs infiltrate the central nervous system (CNS), mediate inflammation, and have a disease exacerbating role by influencing the recruitment of autoreactive T-cells. Elucidating the detailed role of ILCs and altered signaling pathways in MS is essential for a more complete picture of the disease pathology and novel therapeutic targets. We here review the current knowledge about ILCs in the development and progression of MS and preclinical models of MS and discuss their potential for therapeutic applications.

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Section: Role Of Ilcs In Ms: Lessons Learned From Dmtssupporting

confidence: 90%

Section: Role Of Ilcs In Ms: Lessons Learned From Dmtsmentioning

confidence: 99%

Section: Role Of Ilcs In Ms: Lessons Learned From Dmtsmentioning

confidence: 99%

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Innate Lymphoid Cells - Neglected Players in Multiple Sclerosis

et al. 2022

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“…Treatment-related enrichment of a particular NK cell subset, mostly CD56 bright , or induction of NK cell activation has been associated with the therapeutic success of numerous MS drugs including interferon-beta, daclizumab, mitoxantrone, glatiramer acetate, or alemtuzumab [36,[48][49][50][51][52][53][54][55][56][57][58][59].…”

Section: Introductionmentioning

confidence: 99%

“…Effects of fingolimod on NK cells have also been extensively investigated [22,52,[60][61][62][63][64][65][66][67][68][69][70]. Apart from one study that did not observe any significant effect of fingolimod on NK cells [22], all other cross-sectional studies have shown a relative increase of NK cells compared with other lymphocyte populations.…”

Section: Introductionmentioning

confidence: 99%

Fingolimod Therapy in Multiple Sclerosis Leads to the Enrichment of a Subpopulation of Aged NK Cells

et al. 2021

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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 CD56dimCD94low mature NK cells, while the CD56bright 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 CD56dimCD16++KIR+/−NKG2A−CD94−CCR7+/−CX3CR1+/−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.

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Lessons from S1P receptor targeting in multiple sclerosis

Colombo

Farina

2022

Pharmacology & Therapeutics

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

Cited by 7 publications

References 36 publications

Innate Lymphoid Cells - Neglected Players in Multiple Sclerosis

Innate Lymphoid Cells - Neglected Players in Multiple Sclerosis

Fingolimod Therapy in Multiple Sclerosis Leads to the Enrichment of a Subpopulation of Aged NK Cells

Lessons from S1P receptor targeting in multiple sclerosis

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