In Vivo Development of Immune Tissue in Human Intestinal Organoids Transplanted into Humanized Mice

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2023 Jan 26

PMID 36702898

Authors

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

Affiliations

Soon will be listed here.

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.

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