Role of Extracellular Vesicles in Autoimmune Pathogenesis

Wu, Wei; Song, Sheng-Jiao; Zhang, Yuan; Li, Xing

doi:10.3389/fimmu.2020.579043

Cited by 42 publications

(34 citation statements)

References 107 publications

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“…PMP levels are found to be increased in patients with ITP [50,51]. These findings are consistent with other autoimmune mediated disorders, as higher levels of PMPs have also been observed in SLE and RA [52,69,70]. Interestingly, PMPs are suggested to be rapidly cleared from the circulation through mechanisms that are not yet understood, but may involve lactadherin [71,72].…”

Section: Increased Levels Of Pmps In Itpsupporting

confidence: 80%

“…ITP has been associated with higher PMP levels [50,51] and previous reports have primarily focused on their hemostatic role, proposing that their elevated levels in ITP may be a compensatory mechanism to reduce bleeding [50]. Interestingly, however, accumulating literature suggests that PMPs also have immune-modulating functions and might be involved in the development of autoimmune mediated diseases such as SLE and RA [52,53]. Furthermore, PMPs were shown to infiltrate the bone marrow during inflammation and to alter megakaryopoiesis [54,55].…”

Section: Hypothesis 2: Platelet Microparticles In Itpmentioning

confidence: 99%

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Platelets in ITP: Victims in Charge of Their Own Fate?

Nelson

Jolink

Amini

et al. 2021

Cells

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Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder. The pathophysiological mechanisms leading to low platelet levels in ITP have not been resolved, but at least involve autoantibody-dependent and/or cytotoxic T cell mediated platelet clearance and impaired megakaryopoiesis. In addition, T cell imbalances involving T regulatory cells (Tregs) also appear to play an important role. Intriguingly, over the past years it has become evident that platelets not only mediate hemostasis, but are able to modulate inflammatory and immunological processes upon activation. Platelets, therefore, might play an immuno-modulatory role in the pathogenesis and pathophysiology of ITP. In this respect, we propose several possible pathways in which platelets themselves may participate in the immune response in ITP. First, we will elaborate on how platelets might directly promote inflammation or stimulate immune responses in ITP. Second, we will discuss two ways in which platelet microparticles (PMPs) might contribute to the disrupted immune balance and impaired thrombopoiesis by megakaryocytes in ITP. Importantly, from these insights, new starting points for further research and for the design of potential future therapies for ITP can be envisioned.

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Section: Increased Levels Of Pmps In Itpsupporting

confidence: 80%

Section: Hypothesis 2: Platelet Microparticles In Itpmentioning

confidence: 99%

Platelets in ITP: Victims in Charge of Their Own Fate?

Nelson

Jolink

Amini

et al. 2021

Cells

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“…EVs, membranous vesicles released by cells into the interstitial space and circulation, are important mediators of intercellular communication [10–12]. They can functionally transfer proteins, nucleic acids, and metabolites between cells in different physiological (stem cell differentiation [13], innate immunity [14], and reproductive biology [15]) and pathological progression (cancer [16–19], autoimmune disease [20–22], and neurodegeneration [23–25]) processes. Importantly, cardiac cells have also been shown to release EVs into the extracellular space [26] where they can be internalised by neighbouring cardiac fibroblasts and disseminate systemically [27].…”

Section: Figurementioning

confidence: 99%

Proteome characterisation of extracellular vesicles isolated from heart

et al. 2021

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Cardiac intercellular communication is critical for heart function and often dysregulated in cardiovascular diseases. While cardiac extracellular vesicles (cEVs) are emerging mediators of signalling, their isolation remains a technical challenge hindering our understanding of cEV protein composition. Here, we utilised Langendorffcollagenase-based enzymatic perfusion and differential centrifugation to isolate cEVs from mouse heart (yield 3-6 µg/heart). cEVs are ∼200 nm, express classical EV markers (Cd63/81/9 + , Tsg101 + , Pdcd6ip/Alix + ), and are depleted of blood (Alb/Fga/Hba) and cardiac damage markers (Mb, Tnnt2, Ldhb). Comparison with mechanically-derived EVs revealed greater detection of EV markers and decreased cardiac damage contaminants. Mass spectrometry-based proteomic profiling revealed 1721 proteins in cEVs, implicated in proteasomal and autophagic proteostasis, glycolysis, and fatty acid metabolism; essential functions often disrupted in cardiac pathologies. There was striking enrichment of 942 proteins in cEVs compared to mouse heart tissue -implicated in EV biogenesis, antioxidant activity, and lipid transport, suggesting active cargo selection and specialised function. Interestingly, cEVs contain marker proteins for cardiomyocytes, cardiac progenitors, B-cells, T-cells, macrophages, smooth muscle cells, endothelial cells, and cardiac fibroblasts, suggesting diverse cellular origin. We present a method of cEV isolation and provide insight into potential functions, enabling future studies into EV roles in cardiac physiology and disease.

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“…EVs released by antigen-presenting cells express MHC-I, MHC-II, and T cell costimulatory molecules that act as antigen presentation platforms [89]. These antigen-presenting cell-derived EVs could also be used as a vector to present myelin antigens to autoreactive T cells in the absence of costimulatory molecules, as a strategy for restoring immune tolerance in a myelin antigen-specific manner in MS [90]. EVs from the immune system are not naturally loaded with myelin antigens.…”

Section: Role Of Extracellular Vesicles As Preventative Treatment For Multiple Sclerosismentioning

confidence: 99%

Potential Roles of Extracellular Vesicles as Biomarkers and a Novel Treatment Approach in Multiple Sclerosis

Gutiérrez-Fernández

Cuesta

Tallón

et al. 2021

IJMS

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Extracellular vesicles (EVs) are a heterogeneous group of bilayer membrane-wrapped molecules that play an important role in cell-to-cell communication, participating in many physiological processes and in the pathogenesis of several diseases, including multiple sclerosis (MS). In recent years, many studies have focused on EVs, with promising results indicating their potential role as biomarkers in MS and helping us better understand the pathogenesis of the disease. Recent evidence suggests that there are novel subpopulations of EVs according to cell origin, with those derived from cells belonging to the nervous and immune systems providing information regarding inflammation, demyelination, axonal damage, astrocyte and microglia reaction, blood–brain barrier permeability, leukocyte transendothelial migration, and ultimately synaptic loss and neuronal death in MS. These biomarkers can also provide insight into disease activity and progression and can differentiate patients’ disease phenotype. This information can enable new pathways for therapeutic target discovery, and consequently the development of novel treatments. Recent evidence also suggests that current disease modifying treatments (DMTs) for MS modify the levels and content of circulating EVs. EVs might also serve as biomarkers to help monitor the response to DMTs, which could improve medical decisions concerning DMT initiation, choice, escalation, and withdrawal. Furthermore, EVs could act not only as biomarkers but also as treatment for brain repair and immunomodulation in MS. EVs are considered excellent delivery vehicles. Studies in progress show that EVs containing myelin antigens could play a pivotal role in inducing antigen-specific tolerance of autoreactive T cells as a novel strategy for the treatment as “EV-based vaccines” for MS. This review explores the breakthrough role of nervous and immune system cell-derived EVs as markers of pathological disease mechanisms and potential biomarkers of treatment response in MS. In addition, this review explores the novel role of EVs as vehicles for antigen delivery as a therapeutic vaccine to restore immune tolerance in MS autoimmunity.

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Role of Extracellular Vesicles in Autoimmune Pathogenesis

Cited by 42 publications

References 107 publications

Platelets in ITP: Victims in Charge of Their Own Fate?

Platelets in ITP: Victims in Charge of Their Own Fate?

Proteome characterisation of extracellular vesicles isolated from heart

Potential Roles of Extracellular Vesicles as Biomarkers and a Novel Treatment Approach in Multiple Sclerosis

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