Apoptotic vesicles ameliorate lupus and arthritis via phosphatidylserine-mediated modulation of T cell receptor signaling
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 gene...
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KeAi Communications Co., Ltd.
2023-07-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X22003292 |
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author | 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 |
author_facet | 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 |
author_sort | Runci Wang |
collection | DOAJ |
description | 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 apoptosis. In 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 activity. ApoVs 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 maintained. Mechanistically, exposed phosphatidylserine (PtdSer/PS) on apoVs mediated the interaction with T cells to disrupt proximal T cell receptor signaling transduction. Remarkably, administration of apoVs prevented Th17 differentiation and memory formation, and ameliorated inflammation and joint erosion in murine arthritis. Collectively, 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. |
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issn | 2452-199X |
language | English |
last_indexed | 2024-04-09T21:56:12Z |
publishDate | 2023-07-01 |
publisher | KeAi Communications Co., Ltd. |
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series | Bioactive Materials |
spelling | doaj.art-41c4116f65ec473caee0416e32fc2ec22023-03-24T04:23:03ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2023-07-0125472484Apoptotic vesicles ameliorate lupus and arthritis via phosphatidylserine-mediated modulation of T cell receptor signalingRunci Wang0Meng Hao1Xiaoxing Kou2Bingdong Sui3Maria Laura Sanmillan4Xiao Zhang5Dawei Liu6Jun Tian7Wenjing Yu8Chider Chen9Ruili Yang10Lingyun Sun11Yi Liu12Claudio Giraudo13Deepak A. Rao14Nan Shen15Songtao Shi16Shanghai Institute of Rheumatology/Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200002, China; Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA; Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610000, China; Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02105, USA; Corresponding author. Shanghai Institute of Rheumatology/Department of Rheumatology, Renji Hospital, Shanghai Jiaotong University School of Medicine, 145 Middle Shandong Rd, Shanghai, 200002, China.South China Center of Craniofacial Stem Cell Research, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510080, ChinaDepartment of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA; South China Center of Craniofacial Stem Cell Research, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510080, ChinaDepartment of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USADepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, 19107, USADepartment of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USADepartment of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USADepartment of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USADepartment of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USADepartment of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USADepartment of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USADepartment of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, ChinaDepartment of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610000, ChinaDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, 19107, USADivision of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02105, USAShanghai Institute of Rheumatology/Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200002, ChinaDepartment of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA; South China Center of Craniofacial Stem Cell Research, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China; Corresponding author. South China Center of Craniofacial Stem Cell Research, Hospital of Stomatology, Guanghua school of Stomatology, Sun Yat-sen University 74 Zhongshan 2Rd, Guangzhou, Guangdong, 510080, China.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 apoptosis. In 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 activity. ApoVs 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 maintained. Mechanistically, exposed phosphatidylserine (PtdSer/PS) on apoVs mediated the interaction with T cells to disrupt proximal T cell receptor signaling transduction. Remarkably, administration of apoVs prevented Th17 differentiation and memory formation, and ameliorated inflammation and joint erosion in murine arthritis. Collectively, 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.http://www.sciencedirect.com/science/article/pii/S2452199X22003292AutoimmunityT cellMSCApoptosisExtracellular vesicles |
spellingShingle | 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 Apoptotic vesicles ameliorate lupus and arthritis via phosphatidylserine-mediated modulation of T cell receptor signaling Bioactive Materials Autoimmunity T cell MSC Apoptosis Extracellular vesicles |
title | Apoptotic vesicles ameliorate lupus and arthritis via phosphatidylserine-mediated modulation of T cell receptor signaling |
title_full | Apoptotic vesicles ameliorate lupus and arthritis via phosphatidylserine-mediated modulation of T cell receptor signaling |
title_fullStr | Apoptotic vesicles ameliorate lupus and arthritis via phosphatidylserine-mediated modulation of T cell receptor signaling |
title_full_unstemmed | Apoptotic vesicles ameliorate lupus and arthritis via phosphatidylserine-mediated modulation of T cell receptor signaling |
title_short | Apoptotic vesicles ameliorate lupus and arthritis via phosphatidylserine-mediated modulation of T cell receptor signaling |
title_sort | apoptotic vesicles ameliorate lupus and arthritis via phosphatidylserine mediated modulation of t cell receptor signaling |
topic | Autoimmunity T cell MSC Apoptosis Extracellular vesicles |
url | http://www.sciencedirect.com/science/article/pii/S2452199X22003292 |
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