人类肠道器官样体移植到人源化小鼠体内，免疫组织在体内发育。
In vivo development of immune tissue in human intestinal organoids transplanted into humanized mice.
发表日期：2023 Jan 26
作者：
Carine Bouffi, Kathryn A Wikenheiser-Brokamp, Praneet Chaturvedi, Nambirajan Sundaram, Gillian R Goddard, Mark Wunderlich, Nicole E Brown, Janet F Staab, Rachel Latanich, Nicholas C Zachos, Emily M Holloway, Maxime M Mahe, Holly M Poling, Simon Vales, Garrett W Fisher, Jason R Spence, James C Mulloy, Aaron M Zorn, James M Wells, Michael A Helmrath
来源：
NATURE BIOTECHNOLOGY
摘要：
来自多能干细胞的人类肠道器官模型（HIOs）为研究人类肠道生殖和生理提供了一个重要的模型，但它们缺乏充分再现人类肠道生物学和疾病复杂性所需的免疫组分。为了解决这个问题并开始解密发育过程中肠道与免疫系统之间的相互作用，我们通过将HIOs移植到具有人性化免疫系统的小鼠肾被囊下，生成了含有免疫细胞的HIOs。我们发现，人类免疫细胞在时间上移动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，在微生物暴露后，上皮微小折叠细胞数量增加，导致HIO腔中免疫细胞活化并分泌IgA抗体。带有人类免疫细胞的这种在体HIO系统为未来研究感染或变态反应驱动的肠道疾病提供了一个框架。 ©2023. 作者。
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.© 2023. The Author(s).