ArticleGastroenterology2020
Retinoic Acid and Lymphotoxin Signaling Promote Differentiation of Human Intestinal M Cells.
Article in Gastroenterology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 50 citations in OpenAlex.
- Human Small Intestinal Organoids Differentiation Protocols Towards All Mature Epithelial Lineages.Methods in molecular biology (Clifton, N.J.) · 2027Article
- BEST4⁺ cells: a potential hub of intestinal ion transport and diarrhea manipulation.Advanced biotechnology · 2026Review
- Flipping the script: Using mucosal immune obstacles to inform vaccine design.PLoS pathogens · 2026Article
- Fibroblast diversity within human gut-associated lymphoid tissues.The Journal of experimental medicine · 2026Article
- Article
- Gut microbiota-M cell co-culture in inflammatory bowel disease and its therapeutic potential in organoid platforms.Frontiers in pharmacology · 2026Review
- SAMD9 senses cytosolic double-stranded nucleic acids in epithelial and mesenchymal cells to induce antiviral immunity.Nature communications · 2025Article
- Innate immune sensing of rotavirus by intestinal epithelial cells leads to diarrhea.Cell host & microbe · 2025Article
- A Multicellular In Vitro Model of the Human Intestine with Immunocompetent Features Highlights Host-Pathogen Interactions During Early Salmonella Typhimurium Infection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Loss of mucin 2 and MHC II molecules causes rare resistance to murine RV infection.Journal of virology · 2025Article
- The intestinal interferon system and specialized enterocytes as putative drivers of HIV latency.Frontiers in immunology · 2025Review
- Organoids as a tool to study the impact of heterogeneity in gastrointestinal epithelium on host-pathogen interactions.Clinical and experimental immunology · 2024Review
- Deciphering the M-cell niche: insights from mouse models on how microfold cells "know" where they are needed.Frontiers in immunology · 2024Review
- Article
- Cracking the intestinal lymphatic system window utilizing oral delivery vehicles for precise therapy.Journal of nanobiotechnology · 2023Review
- Intestinal Peyer's Patches: Structure, Function, and In Vitro Modeling.Tissue engineering and regenerative medicine · 2023Review
- Gastrointestinal organoids in the study of viral infections.American journal of physiology. Gastrointestinal and liver physiology · 2023Review
- Retinoic Acid Promotes the In Vitro Growth, Patterning and Improves the Cellular Composition of Human Pluripotent Stem-Cell-Derived Intestinal Organoids.International journal of molecular sciences · 2022Article
- CD169Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mechanisms for the Invasion and Dissemination ofThe Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2022Review
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsIntestinal microfold (M) cells are a unique subset of intestinal epithelial cells in the Peyer's patches that regulate mucosal immunity, serving as portals for sampling and uptake of luminal antigens. The inability to efficiently develop human M cells in cell culture has impeded studies of the intestinal immune system. We aimed to identify signaling pathways required for differentiation of human M cells and establish a robust culture system using human ileum enteroids.
methodsWe analyzed transcriptome data from mouse Peyer's patches to identify cell populations in close proximity to M cells. We used the human enteroid system to determine which cytokines were required to induce M-cell differentiation. We performed transcriptome, immunofluorescence, scanning electron microscope, and transcytosis experiments to validate the development of phenotypic and functional human M cells.
resultsA combination of retinoic acid and lymphotoxin induced differentiation of glycoprotein 2-positive human M cells, which lack apical microvilli structure. Upregulated expression of innate immune-related genes within M cells correlated with a lack of viral antigens after rotavirus infection. Human M cells, developed in the enteroid system, internalized and transported enteric viruses, such as rotavirus and reovirus, across the intestinal epithelium barrier in the enteroids.
conclusionsWe identified signaling pathways required for differentiation of intestinal M cells, and used this information to create a robust culture method to develop human M cells with capacity for internalization and transport of viruses. Studies of this model might increase our understanding of antigen presentation and the systemic entry of enteric pathogens in the human intestine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.