4.6 Article

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

Journal

ALLERGY
Volume 75, Issue 5, Pages 1205-1216

Publisher

WILEY
DOI: 10.1111/all.14157

Keywords

allergy; apoptosis; asthma; inflammation; T helper cells

Funding

  1. National Natural Science Foundation of China [31570932, 81701589, 81700888, 81870706]
  2. Shenzhen science, technology and innovation committee [KQJSCX20180328095619081, JCYJ20170307162827158, KQTD20170331145453160]

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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.

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