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Published on: January 21, 2018
Specific Ag-guiding nano-vaccines attenuate neutrophil-dominant allergic asthma
Mei-Zhen Zhao1, Yan Li2, Hai-Yang Han2
1Guangdong Provincial Key Laboratory of New Drug Screening, State Key Laboratory of Organ Failure Research, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China; Department of Clinical Laboratory, Longgang E.N.T Hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T., Shenzhen, China.
Abstract:
Polymorphonuclear neutrophils (PMN) are one fraction of the major inflammatory cells in allergic asthma (asthma, in short); the role of PMN in the asthma pathogenesis is not fully understood yet. This study aims to investigate the effects of specific Ag-guiding exosomes on suppressing the neutrophil-dominant airway inflammation. In this study, BALB/c mice were immunized with ovalbumin plus complete Freund adjuvant to induce an asthma model featured with neutrophil-dominant lung inflammation. The Ag specific PMN (sPMN)-targeting exosomes (tExo), that were exosomes carrying a complex of specific Ag/anti-CD64 Ab and Fas ligand, were constructed to be used to alleviate neutrophilic asthma in mice. We found that sPMNs were the major cellular component in bronchoalveolar lavage fluid (BALF) in asthma mice, while less than 3% PMNs in naive control mice. The sPMNs expressed higher levels of CD64, which formed complexes with Ag-specific IgG (sIgG). The sIgG/CD64 complex-carrying PMNs could be activated upon exposing to specific Ags. Exposure to tExos induced Ag-specific PMNs apoptosis. Administration of tExos efficiently suppressed experimental asthma. We conclude that a fraction of sPMN was identified in the airway of asthma mice. The sPMNs could be activated upon exposure to specific Ags. tExos could induce sPMNs apoptosis, that show the translational potential in the treatment of asthma.
Insights
Specific antigen-targeting exosomes induce apoptosis in neutrophils, offering a potential new treatment for neutrophil-dominant asthma. This approach effectively suppressed experimental asthma in mice.
Area of Science:
- Immunology
- Cell Biology
- Respiratory Medicine
Background:
- Neutrophils are key inflammatory cells in asthma, but their precise role in pathogenesis remains unclear.
- Neutrophil-dominant airway inflammation is a significant feature of allergic asthma.
- Current understanding of neutrophil involvement in asthma requires further investigation.
Purpose of the Study:
- To investigate the therapeutic potential of antigen-specific exosomes in suppressing neutrophil-dominant airway inflammation in asthma.
- To explore the mechanism by which targeted exosomes modulate neutrophil activity in an asthma model.
- To identify specific neutrophil subsets involved in asthma pathogenesis.
Main Methods:
- An asthma model was established in BALB/c mice using ovalbumin and complete Freund adjuvant.
- Antigen-specific PMN-targeting exosomes (tExo) were engineered, carrying antigen/anti-CD64 Ab complexes and Fas ligand.
- The effects of tExo on neutrophil apoptosis and asthma suppression were evaluated in vivo.
Main Results:
- Asthma mice exhibited a significant increase in specific PMNs (sPMNs) in bronchoalveolar lavage fluid compared to controls.
- sPMNs expressed higher CD64 levels, forming complexes with antigen-specific IgG, and were activated by specific antigens.
- Administration of tExo induced apoptosis in antigen-specific PMNs and effectively suppressed experimental asthma.
Conclusions:
- A distinct subset of antigen-specific PMNs (sPMNs) is present and activated in the airways of asthma patients.
- Targeted exosomes (tExo) can induce apoptosis in these sPMNs, demonstrating a novel therapeutic strategy.
- This exosome-based approach holds translational potential for treating neutrophil-driven asthma.
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