Zhang Yuan-Yi, Mo Li-Hua, Yang Gui, Liu Jiang-Qi, Liu Zhi-Qiang, Yang Li-Teng, Ran Pi-Xin, Liu Zhi-Gang, Yang Ping-Chang
Department of Respirology & Allergy, Third Affiliated Hospital of Shenzhen University, Shenzhen, China.
Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
World Allergy Organ J. 2021 Feb 24;14(3):100522. doi: 10.1016/j.waojou.2021.100522. eCollection 2021 Mar.
Antigen (Ag)-specific T helper (Th)2 cells play a central role in food allergy (FA) pathogenesis. Methods can be used to eliminate Ag-specific Th2 cells that are currently lacking. This study aims to eliminate the Ag-specific Th2 cells with a novel nanoparticle, the mEV (modified extracellular vesicles, that carry a chimeric antigen peptide, MHC II and caspase 3) in a murine FA model.
mEVs were generated by exposing dendritic cells (DC) to ovalbumin (OVA, a specific Ag) and recombinant caspase 3 (Casp3) in the culture overnight. Exosomes were purified from culture supernatant by the magnetic antibody approach. A murine FA model was developed with OVA as the specific Ag.
Purified mEVs had the molecular markers of extracellular vesicle, CD81, CD63, and CD9, cleaved Casp3 and MHC II/OVA complexes. mEVs specifically bound to the surface of Ag-specific CD4 T cells, induced Ag-specific CD4 T cell apoptosis both and as well as increased regulatory T cells in the intestinal tissues. Administration of mEV efficiently suppressed experimental FA.
mEVs carry Ag/MHC II complexes and Casp3, that can induce Ag-specific Th2 cell apoptosis. Administration of mEV can efficiently suppress experimental FA. The results suggest that the mEVs have the translational potential to be used in the treatment of FA and other allergic diseases.
抗原（Ag）特异性辅助性T细胞2（Th2）在食物过敏（FA）发病机制中起核心作用。目前缺乏可用于清除Ag特异性Th2细胞的方法。本研究旨在利用一种新型纳米颗粒——修饰的细胞外囊泡（mEV，其携带嵌合抗原肽、MHC II和半胱天冬酶3）在小鼠FA模型中清除Ag特异性Th2细胞。
通过在培养物中使树突状细胞（DC）过夜暴露于卵清蛋白（OVA，一种特异性Ag）和重组半胱天冬酶3（Casp3）来生成mEV。通过磁珠抗体法从培养上清液中纯化外泌体。以OVA作为特异性Ag建立小鼠FA模型。
纯化的mEV具有细胞外囊泡的分子标志物CD81、CD63和CD9、裂解的Casp3以及MHC II/OVA复合物。mEV特异性结合Ag特异性CD4 T细胞表面，诱导Ag特异性CD4 T细胞凋亡，并增加肠道组织中的调节性T细胞。给予mEV可有效抑制实验性FA。
mEV携带Ag/MHC II复合物和Casp3，可诱导Ag特异性Th2细胞凋亡。给予mEV可有效抑制实验性FA。结果表明，mEV具有用于治疗FA和其他过敏性疾病的转化潜力。
