Exosome‐Mediated Lectin Pathway and Resistin‐MIF‐AA Metabolism Axis Drive Immune Dysfunction in Immune Thrombocytopenia
Abstract Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by reduced platelet levels and heightened susceptibility to bleeding resulting from augmented autologous platelet destruction and diminished thrombopoiesis. Although antibody‐mediated autoimmune reactions are widely recog...
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Wiley
2025-03-01
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| Online Access: | https://doi.org/10.1002/advs.202412378 |
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| author | Jin Li Xiaoqian Wang Yaoyao Chen Xianlei Sun Liyan Fu Qingxuan Xin Huilin Zhang Bo Qin Nannan Sun Yingmei Li Yan Xu Hui Yang Dawei Huo Yong Dong Shuya Wang Mengyun Zhao Quande Lin Fang Wang Baohong Yue Yanxia Gao Yong Jiang Rongqun Guo |
| author_facet | Jin Li Xiaoqian Wang Yaoyao Chen Xianlei Sun Liyan Fu Qingxuan Xin Huilin Zhang Bo Qin Nannan Sun Yingmei Li Yan Xu Hui Yang Dawei Huo Yong Dong Shuya Wang Mengyun Zhao Quande Lin Fang Wang Baohong Yue Yanxia Gao Yong Jiang Rongqun Guo |
| author_sort | Jin Li |
| collection | DOAJ |
| description | Abstract Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by reduced platelet levels and heightened susceptibility to bleeding resulting from augmented autologous platelet destruction and diminished thrombopoiesis. Although antibody‐mediated autoimmune reactions are widely recognized as primary factors, the precise etiological agents that trigger ITP remain unidentified. The pathogenesis of ITP remains unclear owing to the absence of comprehensive high‐throughput data, except for the belated emergence of autoreactive antibodies. In this study, using flow cytometry (FCM), proteomics, and single‐cell RNA sequencing of samples from patients with ITP, it is shown that exosome‐mediated lectin complement pathway is involved in the pathogenesis of ITP, which triggers and enlarges the complement activation cascade without effective regulation because of downregulated CD55. The activated complement system enhances the immune response and resistin and further Macrophage Migration Inhibitory Factor (MIF) triggers several proinflammatory signaling pathways, which contribute to the survival of hyperactivated immune cells and dysfunctional arachidonic acid (AA) metabolism. The resistin and MIF are also identified as potential contributors to resistance to glucocorticoid therapy. Taken together, the findings indicate that the lectin pathway of the complement system, resistin, MIF, and AA metabolism may serve as promising targets for ITP treatment, offering novel perspectives on potential therapeutic interventions. |
| format | Article |
| id | doaj-art-0aa5a5b493d2437698bc16620e1d1d22 |
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| issn | 2198-3844 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-0aa5a5b493d2437698bc16620e1d1d222025-08-20T02:23:12ZengWileyAdvanced Science2198-38442025-03-011210n/an/a10.1002/advs.202412378Exosome‐Mediated Lectin Pathway and Resistin‐MIF‐AA Metabolism Axis Drive Immune Dysfunction in Immune ThrombocytopeniaJin Li0Xiaoqian Wang1Yaoyao Chen2Xianlei Sun3Liyan Fu4Qingxuan Xin5Huilin Zhang6Bo Qin7Nannan Sun8Yingmei Li9Yan Xu10Hui Yang11Dawei Huo12Yong Dong13Shuya Wang14Mengyun Zhao15Quande Lin16Fang Wang17Baohong Yue18Yanxia Gao19Yong Jiang20Rongqun Guo21Translational Medical Center The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450001 ChinaDepartment of Laboratory Medicine The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450001 ChinaDepartment of Laboratory Medicine The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450001 ChinaBasic Medical Research Center Academy of Medical Sciences Zhengzhou University Zhengzhou Henan 450052 ChinaDepartment of Laboratory Medicine The First Affiliated Hospital of Henan University of Chinese Medicine Zhengzhou Henan 450046 ChinaDepartment of Laboratory Medicine The First Affiliated Hospital of Henan University of Chinese Medicine Zhengzhou Henan 450046 ChinaTranslational Medical Center The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450001 ChinaTranslational Medical Center The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450001 ChinaDepartment of Hematology The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450001 ChinaDepartment of Hematology The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450001 ChinaDepartment of Hematology The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450001 ChinaTranslational Cancer Research Center Peking University First Hospital Beijing 100034 ChinaBone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory Zhejiang University School of Medicine Zhejiang University Hang Zhou Zhejiang 311100 ChinaDepartment of Immunology School of Basic Medical Sciences Chengdu Medical College Chengdu Sichuan 610500 ChinaDepartment of Blood Transfusion The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450001 ChinaDepartment of Hematology The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital Zhengzhou Henan 450000 ChinaDepartment of Hematology The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital Zhengzhou Henan 450000 ChinaDepartment of Hematology The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450001 ChinaDepartment of Laboratory Medicine The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450001 ChinaDepartment of Emergency Medicine The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450001 ChinaHenan International Joint Laboratory of Infection and Immunity The First Affiliated Hospital Zhengzhou University Zhengzhou Henan 450001 ChinaTranslational Medical Center The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450001 ChinaAbstract Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by reduced platelet levels and heightened susceptibility to bleeding resulting from augmented autologous platelet destruction and diminished thrombopoiesis. Although antibody‐mediated autoimmune reactions are widely recognized as primary factors, the precise etiological agents that trigger ITP remain unidentified. The pathogenesis of ITP remains unclear owing to the absence of comprehensive high‐throughput data, except for the belated emergence of autoreactive antibodies. In this study, using flow cytometry (FCM), proteomics, and single‐cell RNA sequencing of samples from patients with ITP, it is shown that exosome‐mediated lectin complement pathway is involved in the pathogenesis of ITP, which triggers and enlarges the complement activation cascade without effective regulation because of downregulated CD55. The activated complement system enhances the immune response and resistin and further Macrophage Migration Inhibitory Factor (MIF) triggers several proinflammatory signaling pathways, which contribute to the survival of hyperactivated immune cells and dysfunctional arachidonic acid (AA) metabolism. The resistin and MIF are also identified as potential contributors to resistance to glucocorticoid therapy. Taken together, the findings indicate that the lectin pathway of the complement system, resistin, MIF, and AA metabolism may serve as promising targets for ITP treatment, offering novel perspectives on potential therapeutic interventions.https://doi.org/10.1002/advs.202412378arachidonic acid metabolismexosomeimmune thrombocytopeniaMIFresistin |
| spellingShingle | Jin Li Xiaoqian Wang Yaoyao Chen Xianlei Sun Liyan Fu Qingxuan Xin Huilin Zhang Bo Qin Nannan Sun Yingmei Li Yan Xu Hui Yang Dawei Huo Yong Dong Shuya Wang Mengyun Zhao Quande Lin Fang Wang Baohong Yue Yanxia Gao Yong Jiang Rongqun Guo Exosome‐Mediated Lectin Pathway and Resistin‐MIF‐AA Metabolism Axis Drive Immune Dysfunction in Immune Thrombocytopenia Advanced Science arachidonic acid metabolism exosome immune thrombocytopenia MIF resistin |
| title | Exosome‐Mediated Lectin Pathway and Resistin‐MIF‐AA Metabolism Axis Drive Immune Dysfunction in Immune Thrombocytopenia |
| title_full | Exosome‐Mediated Lectin Pathway and Resistin‐MIF‐AA Metabolism Axis Drive Immune Dysfunction in Immune Thrombocytopenia |
| title_fullStr | Exosome‐Mediated Lectin Pathway and Resistin‐MIF‐AA Metabolism Axis Drive Immune Dysfunction in Immune Thrombocytopenia |
| title_full_unstemmed | Exosome‐Mediated Lectin Pathway and Resistin‐MIF‐AA Metabolism Axis Drive Immune Dysfunction in Immune Thrombocytopenia |
| title_short | Exosome‐Mediated Lectin Pathway and Resistin‐MIF‐AA Metabolism Axis Drive Immune Dysfunction in Immune Thrombocytopenia |
| title_sort | exosome mediated lectin pathway and resistin mif aa metabolism axis drive immune dysfunction in immune thrombocytopenia |
| topic | arachidonic acid metabolism exosome immune thrombocytopenia MIF resistin |
| url | https://doi.org/10.1002/advs.202412378 |
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