Objective To investigate the role of the exosomes (EX) derived from polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) preconditioned by hypoxia in the treatment of the collagen-induced arthritis (CIA) mouse model. Methods CIA mouse model was induced by bovine type II collagen(Col2) and Freund's adjuvant. PMN-MDSCs were isolated from CIA mouse spleen by magnetic beads. PMN-MDSC-derived exosomes (PMN-MDSC-EXs) were extracted from the supernatant of PMN-MDSCs under normal (210 mL/L O) and hypoxia (10 mL/L O) conditions. PMN-MDSC-EXs were identified by transmission electron microscopy and flow cytometry. The surface-specific markers of PMN-MDSC-EXs were detected by Western blotting, including CD9, CD63, heat shock protein 70 (HSP70), and calnexin. PMN-MDSC-EXs were added to the CD4 T cell proliferation system in vitro to detect immunosuppressive ability. PMN-MDSC-EXs were injected into the CIA mouse model through the tail vein. The clinic scores of joints were recorded every three days, and the joint structures were observed by HE staining. The levels of total IgG, Col2 antibody, interferon γ (IFN-γ), interleukin 17 (IL-17) in the serum were detected by ELISA. The content of miR-29a-3p and miR-93-5p in PMN-MDSC-EXs under normal and hypoxia conditions was detected by real-time quantitative PCR. Results PMN-MDSCs were successfully isolated from the spleens of CIA mice and PMN-MDSC-EXs was prepared under normal and hypoxia conditions. Compared with normal PMN-MDSC-EXs, hypoxia-treated PMN-MDSC-EXs could inhibit the proliferation of CD4 T cells more effectively. The swelling degree of toes, clinical scores, and joint damage in the group of hypoxia-treated PMN-MDSC-EXs were significantly reduced. The levels of total IgG, Col2 antibody, IFN-γ and IL-17 in the serum decreased after the treatment with hypoxia-treated PMN-MDSC-EXs. The content of miR-29a-3p and miR-93-5p in hypoxia-treated PMN-MDSC-EXs was much higher than that in normal PMN-MDSC-EXs. Conclusion Under hypoxia condition, the immunosuppressive ability of PMN-MDSC-EXs is stronger, which can alleviate the arthropathy of CIA mice more effectively.
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Cell Death Dis
January 2025
Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
The involvement of B lymphocytes in the pathogenesis of rheumatoid arthritis (RA) is well-established, with their early and aberrant activation being a crucial factor. However, the mechanisms underlying this abnormal activation in RA remain incompletely understood. In this study, we identified a significant reduction in MAPK4 expression in both RA patients and collagen-induced arthritis (CIA) mouse models, which correlates with disrupted B cell activation.
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January 2025
Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe, Japan.
Objective: We aimed to evaluate microbiome and microbiota-derived C18 dietary polyunsaturated fatty acids (PUFAs), such as conjugated linoleic acid (CLA), and to investigate their differences that correlate with arthritis severity in collagen-induced arthritis (CIA) mice.
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Biochim Biophys Acta Mol Cell Biol Lipids
January 2025
Institute of Biosciences and Applications, National Center for Scientific Research "Demokritos", Agia Paraskevi, Athens, Greece. Electronic address:
Human paraoxonase 1 (PON1), an enzyme bound to high-density lipoprotein (HDL), hydrolyzes oxidized lipids and contributes to HDL atheroprotective functions. Decreased serum paraoxonase and arylesterase activities of PON1 have been reported in patients at increased atherosclerosis risk, such as rheumatoid arthritis patients, and associated with arthritis severity and cardiovascular risk. Agents that can modulate PON1 activity and HDL-mediated effects have not been discovered.
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January 2025
Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, 610041, China.
Background: Rheumatoid arthritis (RA) is a systemic disease that primarily manifests as chronic synovitis of the symmetric small joints. Despite the availability of various targeted drugs for RA, these treatments are limited by adverse reactions, warranting new treatment approaches. Suberosin (SBR), isolated from Plumbago zeylanica-a medicinal plant traditionally used to treat RA in Asia-possesses notable biological activities.
View Article and Find Full Text PDFExp Mol Med
January 2025
Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Th17 cells are activated by STAT3 factors in the nucleus, and these factors are correlated with the pathologic progression of rheumatoid arthritis (RA). Recent studies have demonstrated the presence of STAT3 in mitochondria, but its function is unclear. We investigated the novel role of mitochondrial STAT3 (mitoSTAT3) in Th17 cells and fibroblast-like synoviocytes (FLSs) and analyzed the correlation of mitoSTAT3 with RA.
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