BACKGROUND It is known that the immune tolerance can be naturally established in the intestine, while the mechanism by which the immune tolerance development in the intestine is not fully understood yet. Vasoactive intestinal peptides (VIP) has the immune regulatory functions. This study aims to investigate the role of VIP in the immune tolerance development in the intestine. METHODS Intestinal epithelial cell (IEC)-derived exosomes were prepared. The exosomes carried IL-10 and antigen/MHC II complexes. VIP-deficient (VIPd) mice and wild type mice were employed to test the role of VIP in the development of immune tolerance in the intestine. RESULTS VIPd mice failed to induce type 1 regulatory T cells (Tr1 cells) in the intestine and retarded the establishment of antigen (Ag)-specific immune tolerance. Exposure to VIP in the culture induced IL-10 expression in intestinal epithelial cells (IECs). Exosomes derived from ovalbumin (OVA, used as a specific Ag)/VIP-primed IECs carried IL-10 and OVA/MHC II complexes; these exosomes were designated IL10CARs (IL-10/chimeric antigen receptor-carrying exosomes). IL10CARs could recognize OVA-specific CD4+ T cells and converted OVA-specific CD4± T cells to OVA-specific Tr1 cells. Administration of IL10CARs suppressed experimental food allergy. CONCLUSIONS The data show that IL10CARs are capable of suppressing experimental FA by inducing antigen-specific Tr1 cells, which has the translation potential for FA treatment.

中文翻译：

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外泌体携带IL-10和抗原/MHC II复合物诱导抗原特异性口服耐受

背景技术众所周知，免疫耐受可以在肠道中自然建立，而肠道内免疫耐受发展的机制尚未完全清楚。血管活性肠肽（VIP）具有免疫调节功能。本研究旨在探讨 VIP 在肠道免疫耐受发展中的作用。方法制备肠上皮细胞（IEC）衍生的外泌体。外泌体携带 IL-10 和抗原/MHC II 复合物。VIP 缺陷 (VIPd) 小鼠和野生型小鼠被用来测试 VIP 在肠道免疫耐受发展中的作用。结果 VIPd 小鼠未能在肠道中诱导 1 型调节性 T 细胞（Tr1 细胞），并阻碍抗原 (Ag) 特异性免疫耐受的建立。在培养物中暴露于 VIP 会诱导肠上皮细胞 (IEC) 中的 IL-10 表达。源自卵清蛋白（OVA，用作特定的 Ag）/VIP 引发的 IEC 的外泌体携带 IL-10 和 OVA/MHC II 复合物；这些外泌体被命名为IL10CARs（IL-10/嵌合抗原受体携带外泌体）。IL10CARs 可以识别 OVA 特异性 CD4+ T 细胞并将 OVA 特异性 CD4± T 细胞转化为 OVA 特异性 Tr1 细胞。IL10CARs 的管理抑制了实验性食物过敏。结论 数据表明，IL10CARs 能够通过诱导抗原特异性 Tr1 细胞来抑制实验性 FA，该细胞具有 FA 治疗的翻译潜力。这些外泌体被命名为IL10CARs（IL-10/嵌合抗原受体携带外泌体）。IL10CARs 可以识别 OVA 特异性 CD4+ T 细胞并将 OVA 特异性 CD4± T 细胞转化为 OVA 特异性 Tr1 细胞。IL10CARs 的管理抑制了实验性食物过敏。结论 数据表明，IL10CARs 能够通过诱导抗原特异性 Tr1 细胞来抑制实验性 FA，该细胞具有 FA 治疗的翻译潜力。这些外泌体被命名为IL10CARs（IL-10/嵌合抗原受体携带外泌体）。IL10CARs 可以识别 OVA 特异性 CD4+ T 细胞并将 OVA 特异性 CD4± T 细胞转化为 OVA 特异性 Tr1 细胞。IL10CARs 的管理抑制了实验性食物过敏。结论 数据表明，IL10CARs 能够通过诱导抗原特异性 Tr1 细胞来抑制实验性 FA，该细胞具有 FA 治疗的翻译潜力。