2. Academic Validation
  3. Exosomes derived from M2 macrophages regulate airway inflammation by modulating epithelial cell proliferation and apoptosis

Exosomes derived from M2 macrophages regulate airway inflammation by modulating epithelial cell proliferation and apoptosis

  • J Inflamm (Lond). 2025 May 19;22(1):19. doi: 10.1186/s12950-025-00444-y.
Yinying Ren 1,  Mi Zhou 1,  Yuehan Li 1,  Yan Li 1,  JinYing Xiang 1,  Fang Deng 1,  Zhengxiu Luo 1,  Enmei Liu 1,  Jinyue Yu 2 3,  Zhou Fu 1,  Fengxia Ding 4,  Bo Liu 5
Affiliations

Affiliations

  • 1 Department of Respiratory Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong Dis, Chongqing, 400014, China.
  • 2 Bristol Medical School, University of Bristol, Bristol, UK.
  • 3 Great Ormond Street Institute of Child Health, University College London, London, UK.
  • 4 Department of Respiratory Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong Dis, Chongqing, 400014, China. 482613@hospital.cqmu.edu.cn.
  • 5 Department of Cardiothoracic Surgery, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong Dis, Chongqing, 400014, China. lbcqmu@126.com.
PMID: 40390011 DOI: 10.1186/s12950-025-00444-y
Abstract

Background: Asthma is a chronic inflammatory disease characterized by airway remodeling and immune dysregulation. This study aimed to explore the mechanisms by which M2 macrophage-derived exosomes (M2Φ-Exos) regulate airway inflammation in asthma by modulating epithelial cell proliferation and Apoptosis.

Methods: M2Φ-Exos were extracted and characterized by morphology, size, and marker protein expression. In vitro, the effects of M2Φ-Exos on House Dust Mites (HDM)-stimulated mouse lung epithelial cells (MLE-12s) were evaluated using western blotting to analyze Proliferating Cell Nuclear Antigen (PCNA), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved Caspase-3 expression. In vivo, M2Φ-Exos were administered to HDM-induced asthmatic mice to assess their impact on airway inflammation, epithelial remodeling, and proliferation-apoptosis balance using immunohistochemistry, immunofluorescence, and western blotting. Cytokine levels in lung tissue and bronchoalveolar lavage fluid (BALF) were measured by qRT-PCR and ELISA.

Results: M2Φ-Exos displayed typical cup-shaped morphology, an average diameter of 115.5 nm, and expressed marker proteins CD9, TSG101, and CD63. MLE-12 cells internalized M2Φ-Exos, leading to reduced abnormal proliferation and Apoptosis in HDM-stimulated cells. In asthmatic mice, M2Φ-Exos alleviated airway inflammation and epithelial thickening while reducing PCNA, cleaved Caspase-3, and Bax levels and increasing Bcl-2 expression. M2Φ-Exos suppressed pro-inflammatory cytokines (IL-4, IL-5, IL-13) and Transforming growth factor (TGF)-β, while enhancing anti-inflammatory cytokine IFN-γ and IL-10.

Conclusion: These findings demonstrate that M2Φ-Exos regulate the imbalance in epithelial proliferation and Apoptosis in asthma, reducing inflammation and mitigating tissue remodeling, and provide new insights into potential therapeutic strategies for asthma management.

Keywords

Apoptosis; Asthma; Exosome; M2 macrophage; Proliferation.

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