Immune modulation mediated by extracellular vesicles of intestinal organoids is disrupted by opioids

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.

Automated summary

Extracellular vesicles (EVs) serve as effective mediators of intercellular communication between enterocytes and immune cells, modulating inflammatory responses through microRNA, especially Let-7. Studies using in vitro and murine models demonstrated that EVs derived from intestinal organoids can reduce inflammation and alleviate colitis symptoms, with opioid use exacerbating immune responses in inflammatory diseases.