On The Role of Natural Killer Cells in Neurodegenerative Diseases

Maghazachi, Azzam A.

doi:10.3390/toxins5020363

Cited by 19 publications

(26 citation statements)

References 79 publications

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“…These findings were in line with other observations showing that GA ameliorated clinical EAE scores, and that NK cells from these mice lysed both iDCs and mDCs [16]. These results indicated that one possible mechanism of GA inhibition may be to activate NK cells to lyse DCs (reviewed in [23]). Similarly, recent observations have shown that mitoxantrone, another drug used for treating MS, induces NK cell enrichment and maturation, which was associated with improved clinical response in secondary progressive MS [24].…”

Section: Discussionsupporting

confidence: 90%

A One Year Follow-Up Study of Natural Killer and Dendritic Cells Activities in Multiple Sclerosis Patients Receiving Glatiramer Acetate (GA)

et al. 2013

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BackgroundMultiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease. It is thought to be mediated by CD4+ Th1/Th17 cells. More recently, cells of the innate immune system such as dendritic cells (DCs) and natural killer (NK) cells have been in focus. Glatiramer acetate (GA) is an approved drug for treating MS patients.Methodology/Principal FindingsIn the current study we examined the activities of NK and DCs in nine relapsing remitting MS patients for up to one year after initiation of GA treatment. We observed that NK cells isolated from most of these patients have increased cytotoxic activity against K562 cells. Further analysis showed that the same NK cells lysed both autologous immature (i) and mature (m) DCs. In most patients this increased activity was correlated with increased NK cell activating cytotoxicity receptors such as NKp30, NKp44, NKp46 and NKG2D, and reduced expression of the inhibitory molecule CD158 on the surface of these NK cells. The expression of HLA-DR was increased on iDCs and mDCs in the majority of the patients, but no consistency was observed for the expression of HLA-I or HLA-E. Also, the co-stimulatory receptors CD80, CD83 or CD86 expression was down-regulated on iDCs and mDCs in most cases. Further, the expression of CCR6 was increased on mDCs at later time points of therapy (between 32–48 weeks).Conclusions/SignificanceOur results are the first showing the effects of GA treatment on NK cells in MS patients, which may impact future use of this and other drugs to treat this disease.

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Section: Discussionsupporting

confidence: 90%

A One Year Follow-Up Study of Natural Killer and Dendritic Cells Activities in Multiple Sclerosis Patients Receiving Glatiramer Acetate (GA)

et al. 2013

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“…Along these associations, there have been speculations as to how exactly NK cells mediate their effects, be it positive or negative. One suggested pathway was interactions between NK cells and dendritic cells [97,101] . The cognate and non-cognate interactions among NK cells and DCs have been previously described.…”

Section: Cd56mentioning

confidence: 99%

“…Further research divided these NK cells into even smaller subsets, recognized as NK22 secreting IL-22 and found in lymphoid tissues of the gastrointestinal tract [94] , or NK17/NK1 cells secreting IL-17 and IFN-γ when stimulated with IL-2 [95] . The role of NK cells in autoimmune diseases is being investigated, and is highly debated as both positive and negative associations have been observed [96][97][98][99] . In the EAE model, depletion of NK cells resulted in a severe relapsing EAE, and more pronounced CNS pathology [100][101][102][103] .…”

Section: Cd56mentioning

confidence: 99%

Multiple sclerosis and the role of immune cells

Høglund

Maghazachi

2014

WJEM

137

101

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Multiple sclerosis (MS) is a complex disease with many different immune cells involved in its pathogenesis, and in particular T cells as the most recognized cell type. Recently, the innate immune system has also been researched for its effect on the disease. Hence, cells of the immune system play vital roles in either ameliorating or exacerbating the disease. The genetic and environmental factors, as well as the etiology and pathogenesis are of utmost importance for the development of MS. An insight into the roles play by T cells, B cells, natural killer cells, and dendritic cells in MS and the animal model experimental autoimmune encephalomyelitis, will be presented. Understanding the mechanisms of action for current therapeutic modalities should help developing new therapeutic tools to treat this disease and other autoimmune diseases.

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“…We focused on the perivascular space (PVS) of the brain because this is the vascularized area where autoreactive cells extravasate into the brain parenchyma. 4,5 Normal mice treated with vehicle showed normal PVS with no T cell infiltration or demyelination as determined by H & E staining, shown in Figure 6A. In contrast, EAE mice showed significant demyelinating areas presented as less myelin density, in addition to areas of loss of myelination in the white matter, as determined by Luxol fast staining ( Figure 6).…”

Section: Histopathological Evaluation Of the Cns Inflammation In Eae mentioning

confidence: 96%

“…It is believed that T cells are activated in the periphery, and then enter the CNS through at least two distinct sites including the subarachnoid space via the choroid plexus, or through the perivascular space at the blood-brain barrier. 4,5 On the other hand, B cells play an essential role in MS, both in humans and mouse models, 6 and are considered very important therapeutic targets for this disease. Cells of the B lymphocyte lineage are found to persist in the inflamed MS central nervous system and occupy multiple sub-compartments.…”

Section: Introductionmentioning

confidence: 99%

<p>Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens</p>

Al‐Ani¹,

Raju²,

Hachim³

et al. 2020

JIR

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Objective: To investigate, in detail, the effects of rituximab (RTX), an off-label drug for treating multiple sclerosis (MS) disease on preventing and/or ameliorating experimental autoimmune encephalomyelitis (EAE). Methods: Using bioinformatics analysis of publicly available transcriptomics data, we determined the accumulation of B cells, plasma cells and T cells in different compartments of multiple sclerosis patients (MS) and healthy individual brains. Based on these observations and on the literature search, we dosed RTX in EAE mice either orally, or injected intraperitoneally (IP). The latter route was used either prophylactically (asymptomatic stage; upon the induction of the disease), or therapeutically (acute stage; upon the appearance of the first sign of the disease). Further, we used RTX as a preventive drug either as a single agent or in combination with other routes of administration. Results: Because no complete recovery was observed when RTX was used prophylactically or therapeutically, we devised another protocol of injecting this drug before the onset of the disease and designated this regiment as prevention. We demonstrated that the 20 μg/mouse prevention completely reduced the EAE clinical score, impaired infiltration of T and B cells into the perivascular space of mice brains, along with inhibiting the inflammation and demyelination. However, the 5 and 10 μg/mouse doses although reduced all aspects of inflammation in these mice, their effects were not as potent as the 20 μg/mouse RTX dose. Finally, we combined the 5 μg/mouse prevention treatment with either the prophylactic or therapeutic regimen and observed a robust effect. Conclusion: We observed that combinatorial regimens resulted in further reduction of inflammation, T and B cell extravasation into the brains of EAE mice and improved the remyelination.

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On The Role of Natural Killer Cells in Neurodegenerative Diseases

Cited by 19 publications

References 79 publications

A One Year Follow-Up Study of Natural Killer and Dendritic Cells Activities in Multiple Sclerosis Patients Receiving Glatiramer Acetate (GA)

A One Year Follow-Up Study of Natural Killer and Dendritic Cells Activities in Multiple Sclerosis Patients Receiving Glatiramer Acetate (GA)

Multiple sclerosis and the role of immune cells

<p>Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens</p>

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