Natural killer cells in multiple sclerosis: A review

Mimpen, Max; Smolders, Joost; Hupperts, Raymond; Damoiseaux, Jan

doi:10.1016/j.imlet.2020.02.012

Cited by 42 publications

(44 citation statements)

References 195 publications

(218 reference statements)

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“…When specifically looking at the NK cell subsets, the prognostic value for disease activity seems predominantly driven by the CD56 dim NK cell ratios. Given that the CD56 bright NK cell subset is generally considered to be the regulatory subset and CD56 bright NK cells correlate negatively with IL‐17A + CD4 + T cell proportions, our clinical associations seem to be conflicting with this concept [8]. However, not only CD56 bright NK cells but also CD56 dim NK cells show a capability to kill activated T cells [30].…”

Section: Discussionmentioning

confidence: 99%

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Prognostic value of natural killer cell/T cell ratios for disease activity in multiple sclerosis

Mimpen

Muris

Rolf

et al. 2020

Euro J of Neurology

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Background and purpose Natural killer (NK) cells may play a role in multiple sclerosis (MS). Ratios of NK cells to CD4+ T cells have been proposed as a biomarker for the therapeutic effect of stem cell transplantation in MS. The objectives here were to explore the relevance of this ratio in MS patients by analysing NK and T cell subsets, as well as their prognostic value for disease activity. Methods Baseline peripheral blood mononuclear cells of 50 relapsing–remitting MS patients, participating in our vitamin D supplementation study (SOLARIUM), were analysed with flow cytometry. Disease activity was measured as new magnetic resonance imaging lesions, relapses and mean plasma neurofilament light chain levels after 48 weeks of follow‐up. Results The proportion of NK cells correlated negatively with CD4+ T cells (R = −0.335, p = 0.001) and interleukin 17A (IL‐17A+) CD4+ T cells (R = −0.203, p = 0.043). Participants with magnetic resonance imaging activity or relapses displayed lower NK/IL‐17A+ CD4+ T cell ratios (p =0.025 and p = 0.006, respectively). The NK/IL‐17A+ CD4+ T cell ratio correlated negatively with neurofilament light chain levels (R = −0.320, p = 0.050). Vitamin D supplementation did not affect these ratios. Conclusions Our data suggest a protective role of an expanded NK cell compartment compared to the CD4+ T cell subset fractions in relapsing–remitting MS patients. NK/CD4+ T cell ratios may be a prognostic biomarker for disease activity in MS.

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Section: Discussionmentioning

confidence: 99%

“…More recently, natural killer (NK) cells are under investigation in MS [8]. NK cells show a strong enrichment for expression of the MS susceptibility genes as reported in a recent genome‐wide association study [9].…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of natural killer cell/T cell ratios for disease activity in multiple sclerosis

Mimpen

Muris

Rolf

et al. 2020

Euro J of Neurology

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“…Likewise, Takahashi et al demonstrated, in MS patients, that CD56 bright NK could favor clinical remission, by suppressing the production of IFNγ, by specific autoreactive T effectors and secreting IL-5 ( 57 , 69 , 75 ). Laroni et al observed that CD56 bright NK cells had reduced ability to kill T-cells in MS patients, compared to healthy controls, possibly due to an increased expression of NKG2A ( 69 , 76 ). Thus, impaired cytotoxicity or the inability to secrete cytolytic granules have been correlated to the escape of proinflammatory cells (both T and B lymphocytes, DC and macrophages) from regulatory mechanisms of controls ( 77 ).…”

Section: Natural Killer Cells and Their Role In Autoimmunitymentioning

confidence: 99%

Immunological Drivers in Graves' Disease: NK Cells as a Master Switcher

et al. 2020

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Graves' disease (GD) is a common autoimmune cause of hyperthyroidism, which is eventually related to the generation of IgG antibodies stimulating the thyrotropin receptor. Clinical manifestations of the disease reflect hyperstimulation of the gland, causing thyrocyte hyperplasia (goiter) and excessive thyroid hormone synthesis (hyperthyroidism). The above clinical manifestations are preceded by still partially unraveled pathogenic actions governed by the induction of aberrant phenotype/functions of immune cells. In this review article we investigated the potential contribution of natural killer (NK) cells, based on literature analysis, to discuss the bidirectional interplay with thyroid hormones (TH) in GD progression. We analyzed cellular and molecular NK-cell associated mechanisms potentially impacting on GD, in a view of identification of the main NK-cell subset with highest immunoregulatory role.

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“…The function of NK cells in MS has is controversial, with protective and pathogenic roles in MS patients and in animal model, the experimental autoimmune encephalomyelitis (EAE). 77,78,[86][87][88][89] For instance, blocking the inhibitory receptor NKG2A on NK cells inhibited CNS inflammation and caused remission by NK cell lysis of autoreactive T cells and microglial cells. 90 Additionally, NK cells have shown a regulatory role in EAE where they can improve disease status.…”

Section: Role Of Nk Cells In Multiple Sclerosismentioning

confidence: 99%

“…137 Natalizumab (Tysabri), a drug for MS patients, is an adhesion molecule inhibitor, that blocks α4β1-integrin, a receptor which is crucial in the migration and recruitment of inflammatory activated immune cells into the CNS. 88 Upon natalizumab treatment, there was a reported increase in circulating NK cells, 138 as possible reduction in their migration capacity into the CNS.…”

Section: Effects Of Ms Therapy On Nk Cell Activitymentioning

confidence: 99%

<p>Drugs for Multiple Sclerosis Activate Natural Killer Cells: Do They Protect Against COVID-19 Infection?</p>

Al‐Ani¹,

Elemam²,

Hundt³

et al. 2020

IDR

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COVID-19 infection caused by the newly discovered coronavirus severe acute respiratory distress syndrome virus-19 (SARS-CoV-2) has become a pandemic issue across the globe. There are currently many investigations taking place to look for specific, safe and potent anti-viral agents. Upon transmission and entry into the human body, SARS-CoV-2 triggers multiple immune players to be involved in the fight against the viral infection. Amongst these immune cells are NK cells that possess robust antiviral activity, and which do not require prior sensitization. However, NK cell count and activity were found to be impaired in COVID-19 patients and hence, could become a potential therapeutic target for COVID-19. Several drugs, including glatiramer acetate (GA), vitamin D 3 , dimethyl fumarate (DMF), monomethyl fumarate (MMF), natalizumab, ocrelizumab, and IFN-β, among others have been previously described to increase the biological activities of NK cells especially their cytolytic potential as reported by upregulation of CD107a, and the release of perforin and granzymes. In this review, we propose that such drugs could potentially restore NK cell activity allowing individuals to be more protective against COVID-19 infection and its complications.

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Natural killer cells in multiple sclerosis: A review

Cited by 42 publications

References 195 publications

Prognostic value of natural killer cell/T cell ratios for disease activity in multiple sclerosis

Prognostic value of natural killer cell/T cell ratios for disease activity in multiple sclerosis

Immunological Drivers in Graves' Disease: NK Cells as a Master Switcher

<p>Drugs for Multiple Sclerosis Activate Natural Killer Cells: Do They Protect Against COVID-19 Infection?</p>

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