Exosome‐Mediated Lectin Pathway and Resistin‐MIF‐AA Metabolism Axis Drive Immune Dysfunction in Immune Thrombocytopenia

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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Main Authors: 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
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:Advanced Science
Subjects:
arachidonic acid metabolism
exosome
immune thrombocytopenia
MIF
resistin
Online Access:https://doi.org/10.1002/advs.202412378
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Summary: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.
ISSN:2198-3844

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