Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis

Gjelstrup, Mikkel Carstensen; Stilund, Morten; Petersen, Thor; Møller, Holger Jon; Petersen, Eva Lykke; Christensen, Tove

doi:10.1111/imcb.1025

Cited by 78 publications

(77 citation statements)

References 67 publications

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“…Patients with HT were also characterized by an increased frequency of CD86 + non-classical Mo, which has been previously reported in patients with other autoimmune diseases including multiple sclerosis (37), systemic lupus erythematous (38), and primary biliary cirrhosis (39). Variations in sample material, separation protocols, detection methodology and definition of Mo subsets might explain why we did not detect a parallel reduction of classical Mo as observed in other studies (38,39).…”

Section: Discussionsupporting

confidence: 67%

Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

et al. 2020

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Although there is evidence that autoimmune diseases share similar immunogenetic mechanisms, studies comparing peripheral CD45 + cells from patients with autoimmune endocrine diseases in parallel are limited. In this study, we applied high-dimensional single-cell mass cytometry to phenotypically characterize PBMC from patients with new-onset (N-T1D) and long-standing type 1 diabetes, Hashimoto's thyroiditis (HT), Graves' disease and autoimmune Addison's disease (AD), as well as healthy controls. The frequency of CD20 lo CD27 hi CD38 hi HLA-DR int plasmablasts, CD86 + CD14 lo CD16 + non-classical monocytes and two subsets of CD56 dim HLA-DR + IFN-γ + NK cells were increased in patients with HT. Subsets of CD56 dim CD69 + HLA-DR − NK cells and CD8 + TEMRA cells, both expressing IFN-γ, were expanded and reduced, respectively, in the N-T1D group. In addition, patients with AD were characterized by an increased percentage of central memory CD8 + T cells that expressed CCR4, GATA3, and IL-2. We demonstrate that patients with N-T1D, HT, and AD had altered frequencies of distinct subsets within antigen-presenting and cytotoxic cell lineages. Previously unreported alterations of specific cell subsets were identified in samples from patients with HT and AD. Our study might contribute to a better understanding of shared and diverging immunological features between autoimmune endocrine diseases.

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Section: Discussionsupporting

confidence: 67%

Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

et al. 2020

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“…Similar to our results, lower amounts of CD14++ monocytes have been described in patients with multiple sclerosis (MS) [34] and juvenile idiopathic arthritis (JIA) with enthesitis [35]. Besides, a higher percentage of CD16+ intermediate and non-classical monocytes with a pro-inflammatory phenotype has been described in patients with MS [34], neuromyelitis optica [36], RA [18], SLE [37], ANCA-vasculitis [38], sarcoidosis [39], IgA nephropathy [40], JIA with enthesitis [35], type 1 diabetes mellitus [41], thromboembolism [42], atherosclerosis and stroke [43] which is according to our results. Also, we found that the absolute number of classical monocytes inversely correlated with the disease activity (MYOACT and MITAX), which is according with previous data in patients with RA, where there is a higher percentage of intermediate monocytes during disease activity and a higher proportion of classical monocytes during remission [44].…”

Section: Discussionsupporting

confidence: 92%

TLR expression in peripheral monocyte subsets of patients with idiopathic inflammatory myopathies: association with clinical and immunological features

et al. 2020

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Background: Monocytes and toll-like receptors (TLR) have been found in the inflammatory infiltrate of muscle biopsies in patients with idiopathic inflammatory myopathies (IIM), suggesting an important role of these cells in the pathogenesis of myositis. The monocyte subsets, their TLR expression in peripheral blood and their relationship with the clinical characteristics of patients with IIM has not been addressed. Methods:We recruited 45 patients with IIM diagnosis and 15 age and sex-adjusted healthy controls. We assessed the disease activity and damage, performed a nailfold capillaroscopy and registered the cardio-pulmonary parameters from the medical charts. Monocyte subsets, their expression of TLR2 and TLR4 and the serum Th1/Th2/Th17 cytokines levels were evaluated by flow cytometry. We expressed quantitative variables as medians and interquartile ranges (IQR) or minimum and maximum (min-max). Differences between groups were assessed with Mann-Whitney U and the Kruskal-Wallis tests. Correlation between quantitative variables was assessed with Spearman Rho.Results: Twenty-nine patients were women (64.4%) and 32 (71.1%) had dermatomyositis. In comparison to healthy controls, patients with active IIM had a higher percentage of intermediate monocytes and lower amounts of classical monocytes. Patients with IIM had a higher expression of TLR4 in all their monocyte subsets, regardless of disease activity and prednisone treatment. Serum IL-6 correlated with the TLR2 expression in every monocyte subset and the expression of TLR2 in intermediate monocytes was higher among patients with dysphagia. Subjects with nailfold capillaroscopy abnormalities had a higher amount of TLR2+ classical and non-classical monocytes and those with interstitial lung disease (ILD) had a higher percentage of TLR4+ non-classical monocytes. The classical and intermediate monocytes from patients with anti Mi2 antibodies had a higher expression of TLR4. The percentage of intermediate monocytes and the expression of TLR4 in all monocyte subsets showed a good diagnostic capacity in patients with IIM. Conclusion:Patients with IIM have a differential pool of monocyte subsets with an enhanced expression of TLR2 and TLR4, which correlates with disease activity and distinctive clinical features including dysphagia, ILD, vasculopathy, and pro-inflammatory cytokines. These immunological features might be useful as a potential diagnostic tool as well as novel disease activity biomarkers in IIM.

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“…In addition, the human genome contains several HERVs followed by poly(A) tails that are in fact LINE-processed pseudogenes from HERV mRNAs (Pavlícek et al 2002). These pseudogenes are remarkably numerous in the HERV-W family, that is one of the most frequently associated with MS (see for example (Gjelstrup et al 2018)). It is therefore tempting to speculate that poly(A) tracts, scars of LINE/SINE retro-transposition events, provide increased stability to some HERV-encoding transcripts and possibly allow for their occasional translation.…”

Section: Discussionmentioning

confidence: 99%

Compound signaling activates endogenous retroviruses by inducing enhancer and gene-neighborhood transcription

Azébi

Batsché

Michel

et al. 2018

Preprint

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SummaryMultiple sclerosis (MS) is a neuroinflammatory and autoimmune disease, in which various immune cell types and autoreactive T cells exert a pathogenic activity. This disease is also associated with increased transcription of several endogenous retroviruses (HERVs) normally kept in check by heterochromatin. Here, we have uncovered an organic pollutant dieldrin that activates several HERVs associated with MS and allowing us to examine the mechanism of their activation. Dieldrin singles out by its ability to simultaneously activate the MAP kinase and the PI3K pathways, while also triggering calcium dependent peptidylarginine deiminase activity. It was this association of pathways that caused HERV activation, a phenomenon that was only part of more generally increased transcription of heterochromatic regions. The HERV transcripts were generally not polyadenylated. Some arose as a consequence of activation of HERV-based enhancers, while others were the result of unusually strong activation at some mostly transcription factor genes causing transcription to leak out of the HERV-free region that surrounds them. Altogether, our data emphasized the hazard associated with simultaneous activation of multiples signaling pathways by xenobiotics, while also providing a very general toolbox for the interpretation of HERV transcription.not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/284695 doi: bioRxiv preprint first posted online Mar. 19, 2018; 2 Introduction Human endogenous retroviruses (HERVs) are vestiges of ancient retroviral infections of the germline. They are present in many more-or-less degenerated copies, classified in families depending on the tRNA used by the original retroviruses to prime the retrotranscription (H for histidine, W for tryptophane, etc.). Together, they represent between 5 and 15% of the human genome. Recently, HERVs have received much attention as next generation sequencing and CRISPR-Cas9 technology have provided evidence for a role of these sequences, together with other potentially transposable element (TE) such as LINEs and Alu sequences, in shaping transcriptional networks. Indeed, TEs are rich in regulatory elements initially necessary for the viral cycle and later possibly co-opted by the host, mostly in the context of immunity and antiviral defense.Historically, HERVs have been also studied for their possible role in the onset of diseases. In particular, several autoimmune diseases including multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis have been associated with increased HERV activity, presence of virus-like particles in the blood, and production of antibodies against HERVencoded proteins (Christensen 2010;Antony et al. 2011). While the role of these HERVs in the onset of autoimmune diseases has been extensively investigated, the mechanisms at the root of their increased transcription in the patients remain essentially unexplored....

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Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis

Cited by 78 publications

References 67 publications

Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

TLR expression in peripheral monocyte subsets of patients with idiopathic inflammatory myopathies: association with clinical and immunological features

Compound signaling activates endogenous retroviruses by inducing enhancer and gene-neighborhood transcription

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