CD8+Treg源性小细胞外囊泡对胶原诱导小鼠关节炎症干预作用的初步研究OA

Objective To investigate the therapeutic efficacy of adoptively transferred sEV in mice with collagen-induced arthritis(CIA),we isolated small extracellular vesicles(sEV)from the culture supernatant of human peripheral blood-derived induced CD8+Treg cells.Methods sEV were isolated via differential ultracentrifugation and characterized by nanoparticle tracking analysis,transmission electron microscopy and western blotting.CIA mice were randomly assigned into control and sEV-treated groups.After intervention,clinical arthritis scoring and histopathological examination of joint tissues were examined.Plasma levels of proinflammatory cytokines and anti-type II collagen antibodies were detected,and CD4+T cell subsets in lymph nodes were quantified by flow cytometry.Results Purified sEV exhibited a typical cup-shaped morphology with an average diameter of 106.8±3.3 nm and expression of CD63 and TSG101.Compared with controls,the sEV-treated group displayed delayed disease onset,alleviated articular inflammation and reduced cartilage erosion.Consistently,plasma TNF-α,IL-6 and anti-type Ⅱ collagen antibodies were markedly reduced,while the frequencies of lymph node CD4+IFN-γ+and CD4+IL-4+T cells were elevated.Conclusion CD8+Treg-derived sEV alleviate joint inflammation in CIA mice by suppressing inflammatory cytokines and modulating CD4+T cell differentiation.