Nakao Koji, Matsuo Tomoe, Shimaoka Iwao, Hara Kosuke
Academic Division, NUTRI Co., Ltd., Shiba, Tokyo 108-0014, Japan.
Biomed Rep. 2025 May 13;23(1):114. doi: 10.3892/br.2025.1992. eCollection 2025 Jul.
Previously, the mechanism underlying the immunostimulatory effect of orally administered heat-killed (HkEf) mediated by exosomes secreted after intestinal macrophage phagocytosis was clarified. In the present study, mouse bone marrow-derived dendritic cells (DCs) were used as intestinal DCs. studies evaluating the response of mouse spleen cells to exosomes purified and isolated from intestinal DCs stimulated with HkEf showed a significant increase in standard DCs and plasmacytoid DCs (pDCs), indicating a positive effect on DCs, mainly pDCs, and possibly contributing to their immunostimulatory effects. The microRNAs (miRNAs) of exosome fractions derived from intestinal DCs and macrophages were also examined using bone marrow progenitor cells. HkEf stimulation released miRNA-rich exosomes, which acted as an immune response signal mediator, and increased various miRNAs other than miR-146 that are essential for refilling innate immune cells. In the present study, the effect mediated by miRNA-rich exosomes on the distant immune system from intestinal immunity (macrophages, DCs) was observed via orally administered HkEf, a preparation. The findings of the present study revealed that this mechanism can potentially prevent systemic infection.
此前,已阐明肠道巨噬细胞吞噬后分泌的外泌体介导口服热灭活大肠杆菌(HkEf)免疫刺激作用的潜在机制。在本研究中,将小鼠骨髓来源的树突状细胞(DCs)用作肠道DCs。评估小鼠脾细胞对从经HkEf刺激的肠道DCs中纯化分离的外泌体反应的研究表明,标准DCs和浆细胞样DCs(pDCs)显著增加,表明对DCs(主要是pDCs)有积极作用,并可能有助于其免疫刺激作用。还使用骨髓祖细胞检查了源自肠道DCs和巨噬细胞的外泌体组分的微小RNA(miRNAs)。HkEf刺激释放了富含miRNA的外泌体,其作为免疫反应信号介质,并增加了除miR-146之外的各种对补充先天免疫细胞至关重要的miRNAs。在本研究中,通过口服制剂HkEf观察到富含miRNA的外泌体对肠道免疫(巨噬细胞、DCs)以外的远端免疫系统的作用。本研究结果表明,该机制可能预防全身感染。