Antibodies Enhance the Suppressive Activity of Extracellular Vesicles in Mouse Delayed-Type Hypersensitivity.
Antibodies Enhance the Suppressive Activity of Extracellular Vesicles in Mouse Delayed-Type Hypersensitivity.
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DOI：
10.3390/ph14080734
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发表时间：
2021-07-27
期刊：
影响因子：
--
通讯作者：
Bryniarski K
中科院分区：
文献类型：
--
作者：
Nazimek K;Bustos-Morán E;Blas-Rus N;Nowak B;Totoń-Żurańska J;Seweryn MT;Wołkow P;Woźnicka O;Szatanek R;Siedlar M;Askenase PW;Sánchez-Madrid F;Bryniarski K
先前，我们发现小鼠延迟型超敏反应（DTH）可以被靶向抗原呈递巨噬细胞的细胞外囊泡（ev）携带的抑制性T细胞来源的miRNA-150特异性下调。然而，mirna -150靶向巨噬细胞对效应T细胞的抑制作用的确切机制尚不清楚，我们目前的研究旨在对此进行研究。通过DTH小鼠模型，我们发现巨噬细胞释放的ev以mirna -150依赖的方式抑制效应T细胞。这种效果通过与抗原特异性抗体的ev预孵育而增强。流式细胞术和elisa实验证实了它们与表达MHCⅱ类的ev的特异性结合。此外，通过纳米颗粒跟踪分析和透射电镜，我们发现巨噬细胞释放的ev与抗原特异性抗体孵养导致ev聚集，这显著增强了它们在体内的抑制活性。如今，越来越多的证据表明，电动汽车在细胞间通讯和选择性货物转运中发挥着特殊作用，因此被认为是治疗用途的有希望的候选者。然而，电动汽车似乎不如它们的亲本细胞有效。在此背景下，我们目前的研究表明，抗原特异性抗体可以很容易地提高ev的生物活性，具有很大的治疗潜力。
Previously, we showed that mouse delayed-type hypersensitivity (DTH) can be antigen-specifically downregulated by suppressor T cell-derived miRNA-150 carried by extracellular vesicles (EVs) that target antigen-presenting macrophages. However, the exact mechanism of the suppressive action of miRNA-150-targeted macrophages on effector T cells remained unclear, and our current studies aimed to investigate it. By employing the DTH mouse model, we showed that effector T cells were inhibited by macrophage-released EVs in a miRNA-150-dependent manner. This effect was enhanced by the pre-incubation of EVs with antigen-specific antibodies. Their specific binding to MHC class II-expressing EVs was proved in flow cytometry and ELISA-based experiments. Furthermore, by the use of nanoparticle tracking analysis and transmission electron microscopy, we found that the incubation of macrophage-released EVs with antigen-specific antibodies resulted in EVs’ aggregation, which significantly enhanced their suppressive activity in vivo. Nowadays, it is increasingly evident that EVs play an exceptional role in intercellular communication and selective cargo transfer, and thus are considered promising candidates for therapeutic usage. However, EVs appear to be less effective than their parental cells. In this context, our current studies provide evidence that antigen-specific antibodies can be easily used for increasing EVs’ biological activity, which has great therapeutic potential.
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影响因子：
7.3
作者：
Andreu Z;Yáñez-Mó M
通讯作者：
Yáñez-Mó M
DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
影响因子：
16
作者：
Crescitelli R;Lässer C;Szabó TG;Kittel A;Eldh M;Dianzani I;Buzás EI;Lötvall J
通讯作者：
Lötvall J
影响因子：
4
作者：
Bustos-Moran, Eugenio;Blas-Rus, Noelia;Sanchez-Madrid, Francisco
通讯作者：
Sanchez-Madrid, Francisco
无标记的单个细胞外囊泡和功能性纳米颗粒的联合形态化学分析
影响因子：
7.4
作者：
Dai, Yichuan;Bai, Suwen;Smith, Zachary J.
通讯作者：
Smith, Zachary J.