In vivo development of immune tissue in human intestinal organoids transplanted into humanized mice.
Journal
Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
04
03
2021
accepted:
07
10
2022
medline:
15
6
2023
pubmed:
27
1
2023
entrez:
26
1
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36702898
doi: 10.1038/s41587-022-01558-x
pii: 10.1038/s41587-022-01558-x
pmc: PMC10264243
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
824-831Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM145304
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK085532
Pays : United States
Organisme : NIH HHS
ID : S10 OD025045
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK103141
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK103117
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK085532
Pays : United States
Informations de copyright
© 2023. The Author(s).
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