Human intestinal organoids (HIOs) derived from pluripotent stem cells provide a valuable model for investigating human intestinal organogenesis and physiology, but they lack the immune components required to fully recapitulate the complexity of human intestinal biology and diseases. To address this issue and to begin to decipher human intestinal–immune crosstalk during development, we generated HIOs containing immune cells by transplanting HIOs under the kidney capsule of mice with a humanized immune system. We found that human immune cells temporally migrate to the mucosa and form cellular aggregates that resemble human intestinal lymphoid follicles. Moreover, after microbial exposure, epithelial microfold cells are increased in number, leading to immune cell activation determined by the secretion of IgA antibodies in the HIO lumen. This in vivo HIO system with human immune cells provides a framework for future studies on infection- or allergen-driven intestinal diseases.

源自多能干细胞的人类肠道类器官（HIO）为研究人类肠道器官发生和生理学提供了有价值的模型，但它们缺乏完全重现人类肠道生物学和疾病复杂性所需的免疫成分。为了解决这个问题并开始破译发育过程中的人类肠道免疫串扰，我们通过将 HIO 移植到具有人源化免疫系统的小鼠的肾囊下，产生了含有免疫细胞的 HIO。我们发现人类免疫细胞暂时迁移到粘膜并形成类似于人类肠道淋巴滤泡的细胞聚集体。此外，接触微生物后，上皮微褶皱细胞数量增加，导致 HIO 腔内 IgA 抗体分泌所决定的免疫细胞活化。这种具有人类免疫细胞的体内 HIO 系统为未来研究感染或过敏原驱动的肠道疾病提供了框架。