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在体人肠类器官移植入人源化小鼠后免疫组织的发育。

In vivo development of immune tissue in human intestinal organoids transplanted into humanized mice.

机构信息

Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

出版信息

Nat Biotechnol. 2023 Jun;41(6):824-831. doi: 10.1038/s41587-022-01558-x. Epub 2023 Jan 26.

DOI:10.1038/s41587-022-01558-x
PMID:36702898
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10264243/
Abstract

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.

摘要

人肠类器官（HIOs）来源于多能干细胞，为研究人类肠道器官发生和生理学提供了有价值的模型，但它们缺乏免疫成分，无法完全重现人类肠道生物学和疾病的复杂性。为了解决这个问题，并开始阐明人类肠道-免疫相互作用在发育过程中的作用，我们通过将 HIO 移植到具有人源化免疫系统的小鼠肾囊下，生成了含有免疫细胞的 HIO。我们发现，人类免疫细胞会暂时迁移到黏膜，并形成类似于人类肠道淋巴滤泡的细胞聚集物。此外，在微生物暴露后，上皮微褶皱细胞的数量增加，导致免疫细胞被激活，这可以通过 HIO 腔中 IgA 抗体的分泌来确定。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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1a7/10264243/49a0860ce465/41587_2022_1558_Fig15_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1a7/10264243/6083507c43b5/41587_2022_1558_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1a7/10264243/09da3acf71a0/41587_2022_1558_Fig6_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1a7/10264243/c1883d2c33ff/41587_2022_1558_Fig7_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1a7/10264243/a16635761e99/41587_2022_1558_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1a7/10264243/e867125e3726/41587_2022_1558_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1a7/10264243/c3b3689c7e7d/41587_2022_1558_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1a7/10264243/a8c36b3061ce/41587_2022_1558_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1a7/10264243/d8da000f48f4/41587_2022_1558_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1a7/10264243/3ed2c9c88165/41587_2022_1558_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1a7/10264243/b15084f08f87/41587_2022_1558_Fig14_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1a7/10264243/49a0860ce465/41587_2022_1558_Fig15_ESM.jpg

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