CARsomes inhibit airway allergic inflammation in mice by inducing antigen-specific Th2 cell apoptosis

被引:8
作者
Zhang, Huan-Ping [1 ]
Sun, Ying-Xue [2 ]
Lin, Zhi [1 ]
Yang, Gui [3 ]
Liu, Jiang-Qi [3 ]
Mo, Li-Hua [4 ]
Geng, Xiao-Rui [3 ]
Song, Yan-Nan [3 ]
Zeng, Hao-Tao [3 ]
Zhao, Miao [3 ]
Li, Guo-Shun [1 ]
Liu, Zhi-Gang [3 ]
Yang, Ping-Chang [3 ]
机构
[1] Shanxi Med Univ, Dept Pulm & Crit Care Med PCCM, Hosp 1, Taiyuan, Peoples R China
[2] Univ Western Ontario, Dept Microbiol & Immunobiol, London, ON, Canada
[3] Shenzhen Univ, ENT Inst Res Ctr Allergy & Immunol, Sch Med, Shenzhen, Peoples R China
[4] Southern Med Univ, Shenzhen Hosp, Dept Pediat Otolaryngol, Shenzhen, Peoples R China
基金
中国国家自然科学基金;
关键词
allergy; apoptosis; asthma; inflammation; T helper cells; REGULATORY T-CELLS; ASTHMA; IMMUNOTHERAPY; ACTIVATION; INDUCTION; PATHWAYS;
D O I
10.1111/all.14157
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background Skewed T helper (Th)2 response plays a crucial role in the pathogenesis of allergic diseases. The therapeutic efficacy for allergic diseases is unsatisfactory currently. This study aims to regulate the skewed Th2 response with CARsomes. Methods The CARsome consisted of an epitope of Dermatophagoides farina-1 (Derf1), a segment of the anti-DEC205 antibody, the scFv, and an open reading frame of perforin. This fusion protein binds to DEC205 molecule on the surface of exosomes derived from dendritic cells (DC). The effects of CARsome on inducing antigen (Ag)-specific Th2 cell apoptosis were assessed both in vivo and in vitro. Results Exposure to CARsomes in the culture induced Ag-specific Th2 cell apoptosis. Injection of CARsomes through the vein puncture also induced Ag-specific Th2 cell apoptosis in the lungs of sensitized mice. CARsomes could induce Ag-specific regulatory T cells. Administration of CARsomes efficiently inhibited experimental allergic airway inflammation. Conclusions The CARsomes can inhibit allergic airway inflammation by inducing Ag-specific Th2 cell apoptosis and induce Ag-specific regulatory T cells. The data suggest that CARsomes have the translational potential to be used to treat allergic airway inflammation.
引用
收藏
页码:1205 / 1216
页数:12
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