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Apoptotic vesicles ameliorate lupus and arthritis via phosphatidylserine-mediated modulation of T cell receptor signaling

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生物活性材料(英文) 2023年第7期25卷 472-484页

作者： Runci Wang Meng Hao Xiaoxing Kou Bingdong Sui maria laura sanmillan Xiao Zhang Dawei Liu Jun Tian Wenjing Yu Chider Chen Ruili Yang Lingyun Sun Yi Liu Claudio Giraudo Deepak A.Rao Nan Shen Songtao Shi Shanghai Institute of Rheumatology/Department of Rheumatology Renji HospitalShanghai Jiao Tong University School of MedicineShanghai200002China Department of Anatomy and Cell Biology School of Dental MedicineUniversity of PennsylvaniaPhiladelphiaPA19104USA Department of Rheumatology and Immunology West China HospitalSichuan UniversityChengduSichuan610000China Division of Rheumatology Inflammation and ImmunityBrigham and Women’s Hospital and Harvard Medical SchoolBostonMA02105USA South China Center of Craniofacial Stem Cell Research Hospital of StomatologyGuanghua School of StomatologySun Yat-sen UniversityGuangzhouGuangdong510080China Department of Microbiology and Immunology Sidney Kimmel Medical CollegeThomas Jefferson UniversityPhiladelphiaPA19107USA Department of Rheumatology and Immunology The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingJiangsu210008China

Mesenchymal stem cells(MSCs)influence T cells in health,disease and therapy through messengers of intercellular communication including extracellular vesicles(EVs).Apoptosis is a mode of cell death that tends to promote immune tolerance,and a large number of apoptotic vesicles(apoVs)are generated from MSCs during *** an effort to characterize these apoVs and explore their immunomodulatory potential,here we show that after replenishing them systemically,the apoV deficiency in Fas mutant mice and pathological lymphoproliferation were rescued,leading to the amelioration of inflammation and lupus *** directly interacted with CD4^(+)T cells and inhibited CD25 expression and IL-2 production in a dose-dependent manner.A broad range of Th1/2/17 subsets and cytokines including IFNγ,IL17A and IL-10 were suppressed while Foxp3^(+)cells were ***,exposed phosphatidylserine(PtdSer/PS)on apoVs mediated the interaction with T cells to disrupt proximal T cell receptor signaling ***,administration of apoVs prevented Th17 differentiation and memory formation,and ameliorated inflammation and joint erosion in murine ***,our findings unveil a previously unrecognized crosstalk between MSC apoVs and CD4^(+)T cells and suggest a promising therapeutic use of apoVs for autoimmune diseases.

关键词： Autoimmunity T cell MSC Apoptosis Extracellular vesicles

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