In vivo development of immune tissue in human intestinal organoids transplanted into humanized mice.
In vivo development of immune tissue in human intestinal organoids transplanted into humanized mice.
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DOI：
10.1038/s41587-022-01558-x
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发表时间：
2023-06
影响因子：
46.9
通讯作者：
Helmrath, Michael A.
中科院分区：
文献类型：
--
作者：
Bouffi, Carine;Wikenheiser-Brokamp, Kathryn A.;Chaturvedi, Praneet;Sundaram, Nambirajan;Goddard, Gillian R.;Wunderlich, Mark;Brown, Nicole E.;Staab, Janet F.;Latanich, Rachel;Zachos, Nicholas C.;Holloway, Emily M.;Mahe, Maxime M.;Poling, Holly M.;Vales, Simon;Fisher, Garrett W.;Spence, Jason R.;Mulloy, James C.;Zorn, Aaron M.;Wells, James M.;Helmrath, Michael A.
来源于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，但它们缺乏完全概括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，并开始破译人类发育过程中的免疫串扰，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来产生含有免疫细胞的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淋巴滤泡的细胞聚集体。此外，在微生物暴露后，上皮微折叠细胞的数量增加，导致免疫细胞活化，其由HIO腔中伊加抗体的分泌决定。这种具有人类免疫细胞的体内HIO系统为感染或过敏原驱动的肠道疾病的未来研究提供了框架。人类肠道类器官通过移植到人源化小鼠中而被赋予免疫细胞。
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. Human intestinal organoids are endowed with immune cells by transplantation into humanized mice.
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影响因子：
28.1
作者：
Poling HM;Wu D;Brown N;Baker M;Hausfeld TA;Huynh N;Chaffron S;Dunn JCY;Hogan SP;Wells JM;Helmrath MA;Mahe MM
通讯作者：
Mahe MM
DOI：
10.1016/j.jaci.2015.09.019
发表时间：
2016-04
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Lee JB;Chen CY;Liu B;Mugge L;Angkasekwinai P;Facchinetti V;Dong C;Liu YJ;Rothenberg ME;Hogan SP;Finkelman FD;Wang YH
通讯作者：
Wang YH
影响因子：
14.8
作者：
通讯作者：
--
影响因子：
11.8
作者：
Spence, Jason R.;Lange, Alex W.;Lin, Suh-Chin J.;Kaestner, Klaus H.;Lowy, Andrew M.;Kim, Injune;Whitsett, Jeffrey A.;Wells, James M.
通讯作者：
Wells, James M.
影响因子：
4.9
作者：
Koboziev I;Jones-Hall Y;Valentine JF;Webb CR;Furr KL;Grisham MB
通讯作者：
Grisham MB