Abstract
AbstractHuman 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.
Funder
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases
Publisher
Springer Science and Business Media LLC
Subject
Biomedical Engineering,Molecular Medicine,Applied Microbiology and Biotechnology,Bioengineering,Biotechnology
Cited by
20 articles.
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