Extracellular vesicles (EVs) are effective mediators of intercellular communications between enterocytes and immune cells. The current study showed that EVs isolated from mouse and human intestinal organoids modulated inflammatory responses of various immune cells including mouse bone-marrow derived-macrophages, dendritic cells, microglia cells, and human monocytes. EVs suppressed LPS-elicited cytokine production in these cells while morphine abolished EVs’ immune modulatory effects. Microarray analysis showed that various microRNAs, especially Let-7, contributed to EV-mediated immune modulation. Using murine models, we showed that injection of EVs derived from intestinal organoids reduced endotoxin-induced systemic inflammation and alleviated the symptoms of DSS-induced colitis. EVs derived from morphine-treated organoids failed to suppress the immune response in both these models. Our study suggests that EVs derived from intestinal crypt cells play crucial roles in maintaining host homeostasis and opioid use is a risk factor for exacerbating inflammation in patients with inflammatory diseases such as sepsis and colitis.

细胞外囊泡（EV）是肠细胞和免疫细胞之间细胞间通讯的有效介质。目前的研究表明，从小鼠和人类肠道类器官中分离出的EV可调节多种免疫细胞的炎症反应，包括小鼠骨髓源性巨噬细胞、树突状细胞、小胶质细胞和人类单核细胞。 EV 抑制了这些细胞中 LPS 引发的细胞因子的产生，而吗啡则消除了 EV 的免疫调节作用。微阵列分析表明，各种 microRNA，尤其是 Let-7，有助于 EV 介导的免疫调节。使用小鼠模型，我们发现注射源自肠道类器官的 EV 可减少内毒素诱导的全身炎症，并减轻 DSS 诱导的结肠炎的症状。在这两种模型中，源自吗啡处理的类器官的 EV 均未能抑制免疫反应。我们的研究表明，源自肠隐窝细胞的 EV 在维持宿主体内平衡中发挥着至关重要的作用，而阿片类药物的使用是加剧脓毒症和结肠炎等炎症性疾病患者炎症的危险因素。