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

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.

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Publication Details

Journal
Advanced Science
Published
2025-01-10
DOI
https://doi.org/10.1002/advs.202412378
Citations
13
Primary Topic
Macrophage Migration Inhibitory Factor
Type
article
Field-Weighted Citation Impact
10.37

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article

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

Yong Dong, Baohong Yue, Yingmei Li, Rongqun Guo et al.
13 citations
Advanced Science
Macrophage Migration Inhibitory Factor
10.37
article

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

Yong Dong, Baohong Yue, Yingmei Li, Rongqun Guo, Liyan Fu, Nannan Sun, Huixia Yang, Yanxia Gao, Dawei Huo, Yong Jiang, Yan Xu, Shuya Wang, Xiaoqian Wang, Huilin Zhang, Mengyun Zhao, Bo Qin, Quande Lin, Qingxuan Xin, Jin Li, Yaoyao Chen, Xianlei Sun, Fang Wang
article en
13 citations

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.

Advanced ScienceVol. 12(10)
Peking University (CN), Chengdu Medical College (CN), Zhengzhou University (CN), Henan Academy of Sciences (CN), Peking University First Hospital (CN), Henan Cancer Hospital (CN), First Affiliated Hospital of Henan University (CN), First Affiliated Hospital of Zhengzhou University (CN), Zhejiang University (CN)
National Natural Science Foundation of China, Zhengzhou University, Science and Technology Department of Henan Province, National Key Research and Development Program of China
Openalex Percentile: Top 2%
Macrophage Migration Inhibitory Factor
10.37
DOIOpen Access PDFOpenAlex
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