Monocyte activation in multiple sclerosis

Reder, Anthony T.; Genç, Kürşad; Byskosh, P.V.; Porrini, A.M.

doi:10.1191/135245898678909538

Cited by 9 publications

(10 citation statements)

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“…Finally, although the age ranges of the healthy subjects and MS patients were similar, the means were significantly different as well as the female:male ratio. However, even with these differences, our findings are in line with previous studies comparing total monocyte phenotypes and responses in healthy and MS populations 3 , 11 , 12 . Furthermore, we found no significant correlation between age and cytokine production, suggesting that a difference in age was not responsible for the effects we observed ().…”

Section: Discussionsupporting

confidence: 91%

“…Immune cells have an important role in the pathogenesis of MS, and among them, monocytes and T cells are known as promoters of inflammation during MS 1 , 2 . Previous research has shown that the circulating monocytes of MS patients have characteristics of classically activated monocytes, including the upregulated expression of CD40, CD86, HLA‐DR 3 and inflammatory cytokines, such as interleukin (IL)‐12. The upregulation of these activation markers and cytokines leads to the stimulation and sustained activation of inflammatory T helper type1 (Th1) and Th17 cells, which are key drivers of inflammation during MS 4 , 5 , 6 …”

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confidence: 99%

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Expansion and preferential activation of the CD14⁺CD16⁺ monocyte subset during multiple sclerosis

Chuluundorj

Harding

Abernethy³

et al. 2014

Immunol Cell Biol

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Multiple sclerosis (MS) is an immune-driven, demyelinating disease of the central nervous system (CNS). Although many types of immune cells are involved in disease progression, activated monocytes are believed to be one of the first to arrive to the brain and initiate inflammation. However, little is known about how the two main monocyte subsets, CD14(++)CD16(-) and CD14(+)CD16(+), are involved in MS. To understand how the phenotype and responses of these monocyte subsets are altered during MS, total monocytes and the purified monocyte subsets from healthy subjects (n=29) and MS patients (n=20) were characterized ex vivo and stimulated in vitro with lipopolysaccharide (LPS). The ex vivo analyses showed that total monocytes from MS patients had significantly elevated levels of CD40, CD86, HLA-DR, CD64 and C-C motif chemokine receptor 2 (CCR2), and this elevation was most marked on CD16(+) monocytes. In vitro stimulation with LPS led to an increase in CD86, HLA-DR, CD64 and IL-6 production by monocytes from MS patients. Furthermore, in purified cultures, CD14(+) monocytes were found to be the main producers of IL-10 while CD16(+) monocytes produced more IL-12. In monocytes from MS patients, both subsets produced substantially more IL-6, and the production of IL-10 by the CD16(+) subset was also significantly elevated compared with healthy monocytes. Together these findings highlight the important contribution of the CD16(+) monocyte subset in driving inflammatory responses during MS.

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

Expansion and preferential activation of the CD14⁺CD16⁺ monocyte subset during multiple sclerosis

Chuluundorj

Harding

Abernethy³

et al. 2014

Immunol Cell Biol

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“…Significant differences in full blood count parameters from the MS cohort were observed, and consistent with previous literature on female MS patients, ESR results were significantly increased compared to CFS/ME and non‐fatigued controls . This result suggests that there is significant peripheral inflammation in this cohort of untreated patients with MS. Additional significant increases were reported for lymphocyte and monocyte results in the MS cohort compared to CFS/ME and the non‐fatigued controls; however, previous literature has reported no significant differences . The small sample size may contribute to differences observed in white blood cell parameters in this MS cohort.…”

Section: Discussionmentioning

confidence: 56%

Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis

et al. 2015

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Patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and multiple sclerosis (MS) suffer from debilitating fatigue which is not alleviated by rest. In addition to the fatigue-related symptoms suffered by patients with CFS/ME and MS, dysfunction of the immune system and, in particular, reduced natural killer (NK) cell cytotoxic activity has also been reported in CFS/ME and MS. The purpose of this pilot study was to compare NK cellular mechanisms in patients with CFS/ME and MS to investigate potential dysfunctions in the NK cell activity pathway. Flow cytometry protocols assessed CD56 dim CD16 + and CD56 bright CD16 +/À NK cell expression of adhesion molecules, NK activating and inhibiting receptors, NK cell maturation and lytic proteins. All participants in this study were female and included 14 patients with CFS/ME, nine patients with MS and 19 non-fatigued controls. The patient groups and the non-fatigued controls were not taking any immunosuppressive or immune-enhancing medications. In the MS cohort, KIR2DL5 was significantly increased on CD56 bright CD16 +/À NK cells and expression of CD94 was significantly increased on CD56 dim CD16 + NK cells in comparison with the controls. Co-expression of CD57 and perforin was significantly increased on CD56 dim CD16 + NK cells from patients with CFS/ME compared to the MS and non-fatigued control participants. The results from this pilot study suggest that NK cells from patients with CFS/ME and MS may have undergone increased differentiation in response to external stimuli which may affect different mechanisms in the NK cell cytotoxic activity pathway.

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“…Thus, it is possible that levels of secretion contributed by a minor cell population, such as monocytes of MS patients, are too low to be detected. The expression of TWEAK at the monocyte cell surface could represent a marker of monocyte activation, which has been correlated previously with MS disease activity [18,19], and histological studies in MS brain material clearly suggested that infiltration of activated monocytes plays an important role in lesion formation [20]. Filion et al [21] showed that monocytes of MS patients produced increased levels of soluble proinflammatory cytokine such as IL-1␤, IL-6, and TNF-␣.…”

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confidence: 62%

TWEAK is expressed at the cell surface of monocytes during multiple sclerosis

Desplat‐Jégo

Feuillet

Creidy

et al. 2008

Journal of Leukocyte Biology

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The TNF superfamily ligand, TNF-like weak inducer of apoptosis (TWEAK), regulates cellular responses ranging from proliferation to cell death in a manner highly dependent on the cell type and the microenvironmental context. We have shown previously that treatment of experimental autoimmune encephalomyelitis mice after the priming phase with neutralizing anti-TWEAK antibodies results in a reduction in the severity of the disease and leukocyte infiltration. To further characterize TWEAK/fibroblast growth factor-inducible 14-kDa protein (Fn14) involvement during multiple sclerosis (MS), we evaluated in MS patients and controls: TWEAK and Fn14 expression on PBMC and soluble TWEAK concentration in serum and cerebrospinal fluid (CSF). Thirty-six consecutive patients were enrolled, including 11 patients with relapsing-remitting MS, 11 with a clinical isolated syndrome suggestive of MS (CISSMS), and 14 controls with non-MS diseases. Intracellular TWEAK could be observed in lymphocytes and/or monocytes in all groups of patients. None of the 36 patients displayed TWEAK expression at the cell surface of lymphocytes. In contrast, 12 out of the 36 patients were positive for membrane TWEAK expression on their monocytes. Among these patients, eight were from the CISSMS group. Fn14 was not detected in PBMC. The soluble form of TWEAK is detectable in serum and CSF of patients, and TWEAK concentrations were not statistically different between the disease groups. We demonstrated for the first time that TWEAK is expressed at the cell surface of monocytes during MS, especially in the CISSMS group. Our results support the proposal that TWEAK could be a target for antibody therapy in MS.

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Monocyte activation in multiple sclerosis

Cited by 9 publications

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Expansion and preferential activation of the CD14⁺CD16⁺ monocyte subset during multiple sclerosis

Expansion and preferential activation of the CD14⁺CD16⁺ monocyte subset during multiple sclerosis

Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis

TWEAK is expressed at the cell surface of monocytes during multiple sclerosis

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Monocyte activation in multiple sclerosis

Cited by 9 publications

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Expansion and preferential activation of the CD14+CD16+ monocyte subset during multiple sclerosis

Expansion and preferential activation of the CD14+CD16+ monocyte subset during multiple sclerosis

Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis

TWEAK is expressed at the cell surface of monocytes during multiple sclerosis

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Expansion and preferential activation of the CD14⁺CD16⁺ monocyte subset during multiple sclerosis

Expansion and preferential activation of the CD14⁺CD16⁺ monocyte subset during multiple sclerosis