A Membrane Form of TNF Presented by Exosomes Delays T Cell Activation-Induced Cell Death1 (original) (raw)
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The Role of Cell Organelles in Rheumatoid Arthritis with Focus on Exosomes
Biological Procedures Online, 2021
Auto-immune diseases involved at least 25% of the population in wealthy countries. Several factors including genetic, epigenetic, and environmental elements are implicated in development of Rheumatoid Arthritis as an autoimmune disease. Autoantibodies cause synovial inflammation and arthritis, if left untreated or being under continual external stimulation, could result in chronic inflammation, joint injury, and disability. T- and B-cells, signaling molecules, proinflammatory mediators, and synovium-specific targets are among the new therapeutic targets. Exosomes could be employed as therapeutic vectors in the treatment of autoimmune diseases. Herein, the role of cell organelle particularly exosomes in Rheumatoid Arthritis had discussed and some therapeutic applications of exosome highlighted.
Mediators of inflammation, 2017
The purpose of this study is to characterize synovial fluid- (SF-) derived exosomes of patients with gonarthrosis comparing two methods of isolation and to investigate their immune regulatory properties. Extracellular vesicles (EVs) have been isolated from inflamed SF by polymer precipitation method and quantified by Exocet kit and by nanoparticle tracking analysis. Vesicles expressed all the specific exosomal markers by immunoblot and FACS. After isolation with Exoquick, a relevant contamination by immune complexes was detected, which required further magnetic bead-based purification to remove. SF-derived exosomes significantly stimulated the release of several inflammatory cytokines and chemokines and metalloproteinases by M1 macrophages but did not influence the expression of CD80 and CD86 costimulatory molecules. In conclusion, we characterized purified exosomes isolated from inflamed SF and demonstrate that purified exosomes are functionally active in their ability to stimulate...
Exosomes as Rheumatoid Arthritis Diagnostic Biomarkers and Therapeutic Agents
Vaccines
Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder that causes systemic inflammation, autoimmunity, and joint abnormalities that result in permanent disability. Exosomes are nanosized extracellular particles found in mammals (40–100 nm). They are a transporter of lipids, proteins, and genetic material involved in mammalian cell–cell signaling, biological processes, and cell signaling. Exosomes have been identified as playing a role in rheumatoid arthritis-related joint inflammation (RA). Uniquely functioning extracellular vesicles (EVs) are responsible for the transport of autoantigens and mediators between distant cells. In addition, paracrine factors, such as exosomes, modulate the immunomodulatory function of mesenchymal stem cells (MSCs). In addition to transporting genetic information, exosomes convey miRNAs between cells and have been studied as drug delivery vehicles. In animal models, it has been observed that MSCs secrete EVs with immunomodulatory properties...
Implications of Anti-Inflammatory Nature of Exosomes in Knee Arthritis
CARTILAGE, 2020
Exosomes are extracellular vesicles (EVs) released from cells that are a part of many biological and pathological processes, especially in intercellular communication. These vesicles are involved cell signaling, influence tissue and immune response, and serve as biomarkers for diseases. Most interesting are the exosomes that are released from mesenchymal stem cells (MSCs) for inflammation in joint diseases. Preliminary studies have demonstrated the advantages of using EVs rather than MSCs for cell free therapy. Research on exosomes have shown promising results as biomarkers for tracking the pathogenesis and prognosis of inflammatory arthritis. Therapeutically, animal studies have demonstrated immunosuppression, reversing inflammation, increasing chondrocyte proliferation, and drug delivery properties. The field of exosomes continues to develop and more basic science and clinical studies with safety and efficacy studies are needed.
Erciyes Medical Journal, 2023
Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease that leads to structural and functional impairments and reduced quality of life, with heterogeneous manifestations. The origin and possible role of extracellular vesicles represented by exosomes (EVexo) in the pathogenesis of AS were examined in this study. Materials and Methods: Extracellular vesicles (EVs) were isolated from serum from ten AS patients and ten healthy controls through Izon qEV2/35 nm columns. After assessing the isolate purity by bicinchoninic acid assay (BCA) and Enzyme-Linked ImmunoSorbent Assay (ELISA), the relationship between EVexo concentration and AS was tested by the BCA method. The EVexo surface markers were analyzed by flow cytometry (FC) to verify EVexo presence and reveal its origin. Results: In FC analysis, CD86+TSG101+ and CD3+TSG101+ exosome percentages of AS group were significantly higher than the control group (p<0.05). A significant difference was found between the AS and control groups in terms of CD3+IL17+ and CD3+IFNg+ and CD86+TNFα+ and CD86+IL12(p35)+ exosome percentages (p<0.01). Conclusion: The exosomes whose ratio increased in the AS process were derived from T cells expressing increased levels of IL-17A and IFNg in their membranes, and macrophages expressing increased levels of TNFα and IL-12(p35) in their membranes. The EVexo profile did not change according to the AS course.
Comparison of the Exosome Profile in Ankylosing Spondylitis and Healthy Controls
Erciyes Medical Journal
Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease that leads to structural and functional impairments and reduced quality of life, with heterogeneous manifestations. The origin and possible role of extracellular vesicles represented by exosomes (EVexo) in the pathogenesis of AS were examined in this study. Materials and Methods: Extracellular vesicles (EVs) were isolated from serum from ten AS patients and ten healthy controls through Izon qEV2/35 nm columns. After assessing the isolate purity by bicinchoninic acid assay (BCA) and Enzyme-Linked ImmunoSorbent Assay (ELISA), the relationship between EVexo concentration and AS was tested by the BCA method. The EVexo surface markers were analyzed by flow cytometry (FC) to verify EVexo presence and reveal its origin. Results: In FC analysis, CD86+TSG101+ and CD3+TSG101+ exosome percentages of AS group were significantly higher than the control group (p<0.05). A significant difference was found between the AS and control groups in terms of CD3+IL17+ and CD3+IFNg+ and CD86+TNFα+ and CD86+IL12(p35)+ exosome percentages (p<0.01). Conclusion: The exosomes whose ratio increased in the AS process were derived from T cells expressing increased levels of IL-17A and IFNg in their membranes, and macrophages expressing increased levels of TNFα and IL-12(p35) in their membranes. The EVexo profile did not change according to the AS course.
Theranostics, 2018
Mesenchymal stem cells (MSCs) release extracellular vesicles (EVs) that display a therapeutic effect in inflammatory disease models. Although MSCs can prevent arthritis, the role of MSCs-derived EVs has never been reported in rheumatoid arthritis. This prompted us to compare the function of exosomes (Exos) and microparticles (MPs) isolated from MSCs and investigate their immunomodulatory function in arthritis.MSCs-derived Exos and MPs were isolated by differential ultracentrifugation. Immunosuppressive effects of MPs or Exos were investigated on T and B lymphocytesand in the Delayed-Type Hypersensitivity (DTH) and Collagen-Induced Arthritis (CIA) models.Exos and MPs from MSCs inhibited T lymphocyte proliferation in a dose-dependent manner and decreased the percentage of CD4and CD8T cell subsets. Interestingly, Exos increased Treg cell populations while parental MSCs did not. Conversely, plasmablast differentiation was reduced to a similar extent by MSCs, Exos or MPs. IFN-γ priming o...
Frontiers in Veterinary Science, 2017
Synovitis is an inflammatory process associated with pain, disability, and discomfort, which is usually treated with anti-inflammatory drugs or biological agents. Mesenchymal stem cells (MSCs) have been also successfully used in the treatment of inflammatory-related diseases such as synovitis or arthritis. In the last years, the exosomes derived from MSCs have become a promising tool for the treatment of inflammatory-related diseases and their therapeutic effect is thought to be mediated (at least in part) by their immunomodulatory potential. In this work, we aimed to evaluate the anti-inflammatory effect of these exosomes in an antigen-induced synovitis animal model. To our knowledge, this is the first report where exosomes derived from MSCs have been evaluated in an animal model of synovitis. Our results demonstrated a decrease of synovial lymphocytes together with a downregulation of TNF-α transcripts in those exosome-treated joints. These results support the immunomodulatory effect of these exosomes and point out that they may represent a promising therapeutic option for the treatment of synovitis.