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Microfold (M) cells: important immunosurveillance posts in the intestinal epithelium
Open accessAbstract
The transcytosis of antigens across the gut epithelium by microfold cells (M cells) is important for the induction of efficient immune responses to some mucosal antigens in Peyer's patches. Recently, substantial progress has been made in our understanding of the factors that influence the development and function of M cells. This review highlights these important advances, with particular emphasis on: the host genes which control the functional maturation of M cells; how this knowledge has led to the rapid advance in our understanding of M-cell biology in the steady state and during aging; molecules expressed on M cells which appear to be used as "immunosurveillance" receptors to sample pathogenic microorganisms in the gut; how certain pathogens appear to exploit M cells to infect the host; and finally how this knowledge has been used to specifically target antigens to M cells to attempt to improve the efficacy of mucosal vaccines.
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“Since they have a plasma membrane rich in specific carbohydrate residues, such as α-L fucose and monoganglioside (GM1) [10–12]”
From Characterization of Vibrio cholerae neuraminidase as an immunomodulator for novel formulation of oral allergy immunotherapy (2018) · cites this paper as [12]
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“The enhanced antigen uptake and immune sys-tem activation also facilitate transport through the nasal epithelium via activation of this pathway [178–181].”
Deng, Y., He, X., Peng, J., Pan, Y., Luo, Y., Ruan, Y., Hou, J., Jiang, B., Li, X., Liang, X., et al. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-08007-y · Cited by 8
“In the aging process, the immune system is often characterised by chronic in fl ammation and a diminished defensive capacity, which may contribute to the pathogenesis of various age-associated illnesses [68, 69].”
Microbiome-immune crosstalk in allergic rhinitis: lung and intestinal microbiota mechanisms
Wang, C., Zhai, C., Hu, S., & Lu, Y. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1697226 · Cited by 6
Cuesta‐Marti, C., Ponce‐España, E., Uhlig, F., Stoltenborg, I., Wasiewska, L. A., Kareem, L., Hedayatpour, D., Olavarría‐Ramírez, L., Rosell‐Cardona, C., Bastiaanssen, T. F. S., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-68968-2 · Cited by 5
Liposomes in oral delivery: mechanisms, advances, challenges, and future perspectives
Pan, P., Ma, Y., Kong, S., Ahmed, K. S., & Wu, Z. (2026) · Journal of Liposome Research · doi:10.1080/08982104.2026.2675542 · Cited by 6
Wu, S., Hu, L., Fu, Y., Chen, Y., Hu, Z., Li, H., & Liu, Z. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03807-9 · Cited by 5
“M cells originate from intestinal epithelial stem cells located within the crypts [27], and the decline in M cells may be associated with senescence of intestinal stem cells (ISCs).”
Self-assembly mucoadhesive beads of κ-carrageenan/sericin for indomethacin oral extended release
Vieira, W. T., Viegas, J. S. R., da Silva, M. G. C., Nascimento, L. D. O., Vieira, M. G. A., & Sarmento, B. F. C. C. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.132062 · Cited by 5
Alfituri, O. A., Blake, R., Jensen, K., Mabbott, N. A., Hope, J. C., & Stevens, J. M. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1416537 · Cited by 5
Self-citationTear duct M cells exacerbate allergic conjunctivitis by facilitating germinal-center reactions
Oya, Y., Kimura, S., Uemura, M., Fujimura, Y., & Hase, K. (2025) · Mucosal Immunology · doi:10.1016/j.mucimm.2025.01.009 · Cited by 5
Craner, A. J., Dahlen, C. R., Hurlbert, J. L., Menezes, A. C. B., Banerjee, P., Baumgaertner, F., Bochantin-Winders, K. A., Amat, S., Sedivec, K. K. K., Swanson, K. C., et al. (2025) · Journal of Developmental Origins of Health and Disease · doi:10.1017/s2040174425000157 · Cited by 6
Nakanishi, K., Ajiro, T., Yukishima, K., Tsukamoto, Y., Kikuta, J., Sawa, S., Tomura, M., Kinoshita, N., Shimanuki, W., Suzuki, A., et al. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2536089 · Cited by 5
Cunningham, A. L., Guentzel, M. N., Yu, J., Hung, C.-Y., Forsthuber, T. G., Navara, C. S., Yagita∥, H., Williams, I. R., Klose, K. E., Eaves-Pyles, T. D., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0153402 · Cited by 5
“Several mechanisms of antigen trafficking beside M-cell transcytosis have been reported [27], ranging from extensions of dendritic cell processes through the intestinal epithelial monolayer [28, 29], transepithelial passage [30, 31], translocation through enterocytes [32] and recently, a Role of M-Cells in Oral Tulare…”
BackgroundSelf-citationSato, S., & Pascual, D. W. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-811924-2.00028-6 · Cited by 5
MyD88 Mediates Colitis- and RANKL-Induced Microfold Cell Differentiation
Li, Y., Yang, S., Huang, X. S., Yang, N., Wang, C., Zhao, J., Jing, Z., Willems, L., & Liu, G. (2021) · Veterinary Sciences · doi:10.3390/vetsci9010006 · Cited by 5
“M cells possess unique 50 morphological features, such as irregular brush border, pocket structure, reduced 51 glycocalyx, and microvilli [6].”
BackgroundSong, Y.-J., Liu, H., & Yang, X.-G. (2023) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-023-02033-x · Cited by 5
Gaikwad, V. L., Sen, S. G., & Dhake, P. R. (2024) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2024.105475 · Cited by 5
Shigella: Virulence Factors and Pathogenicity
Bliven, K. A., & Lampel, K. A. (2017) · Springer eBooks · doi:10.1007/978-3-319-56836-2_7 · Cited by 5
“Because of their vital immunological role in routine antigensampling, M cells express a variety of unique ligands that are absent on the apical surface of other intestinal epithelial cells, including glycoprotein 2, uromodulin, and ANXA5 (Mabbott et al. 2013).”
BackgroundÖzbek, M., & BAYRAKTAROĞLU, A. G. (2019) · Acta Histochemica · doi:10.1016/j.acthis.2019.01.005 · Cited by 5
Singh, N., Gallagher, H. C., Song, R., Dhinsa, J. K., Ostroff, G. R., & Jesus, M. D. (2018) · Journal of Biological Methods · doi:10.14440/jbm.2018.246 · Cited by 5
“Below the FAE, in the sub-epithelial dome (SED), there is an extensive and dynamic network of dendritic cell (DCs) and macrophage subsets.”
BackgroundZheng, H. B., Doran, B. A., Kimler, K., Yu, A., Tkachev, V., Niederlová, V., Cribbin, K., Fleming, R., Bratrude, B., Betz, K., et al. (2023) · eLife · doi:10.7554/elife.91792 · Cited by 5
Sun, X., Wu, Y., Han, C., Zhang, N., Chen, X., & Chen, Y. (2024) · Immunology Letters · doi:10.1016/j.imlet.2024.106925 · Cited by 4
Emerging trends in permeation-enhancing technologies for oral peptide delivery
Tao, J., Yang, J., Zhao, M., Zhu, Q., Chen, Z., & Qi, J. (2025) · Chinese Chemical Letters · doi:10.1016/j.cclet.2025.111170 · Cited by 4
Mikami, Y., Kuroda, E., Kimura, S., Hayatsu, M., Watanabe, K., Tsuda, H., Nakamura, Y., Sagawa, T., Ichinose, T., Takano, H., et al. (2025) · Clinical and Experimental Medicine · doi:10.1007/s10238-025-01918-2 · Cited by 4
“Microfold cells (M-cells) responsible for antigen uptake are present in the GALT LE [27].”
Sugandhi, V. V., Gadhave, D. G., Khot, S. V., Jadhav, K., Patel, D., Thapa, R., Verma, R. K., Rojekar, S. V., Patil, N. G., Jha, S. K., et al. (2025) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2025.106960 · Cited by 4
Tang, R., Zeng, F., Lyu, C., Tuerheng, J., Guo, Z., He, K., & Wu, D. (2026) · Pharmaceutics · doi:10.3390/pharmaceutics18050534 · Cited by 4
“More predictive mechanistic models of epithelial transport are therefore needed [180].”
Enhanced Bioavailability and Intestinal Uptake of Nanoparticles After Oral Delivery
Patel, M., & Sawant, K. K. (2022) · Springer eBooks · doi:10.1007/978-3-030-83395-4_21 · Cited by 4
Discrimination of distinct chicken M cell subsets based on CSF1R expression
Zeinali, S., Sutton, K., Zefreh, M. G., Mabbott, N. A., & Vervelde, L. (2024) · Scientific Reports · doi:10.1038/s41598-024-59368-x · Cited by 4
Self-citationHayashi, H., Ohtani, M., Sada, Y., Iwasaki, K., & Shimokawa, I. (2018) · Histopathology · doi:10.1111/his.13639 · Cited by 4
“Recent studies have shown that M cells are derived from intestinal epithelial stem cells as well as other enterocytes, but are influenced specifically by GALT.(5) GALT carcinoma has been hypothesised to originate from M cells because it contains GALT-like lymphoid tissue, lacks goblet cells, and is morphologically sim…”
BackgroundResultInfluentialBaillou, A., Tomal, F., Chaumeil, T., Barc, C., Vern, Y. L., Sausset, A., Pézier, T., Schulthess, J., Peltier, P., Laurent, F., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1379798 · Cited by 4
Human norovirus cultivation models, immune response and vaccine landscape
Burton, T. D., Montoya, J. C., Frota, T., & Mackenzie, J. M. (2024) · Advances in virus research · doi:10.1016/bs.aivir.2024.09.001 · Cited by 5
Metadata
- Authors
- Mabbott, N. A., Donaldson, D. S., Ohno, H., Williams, I. R., & Mahajan, A.
- Affiliations
- Roslin Institute (GB)
- RIKEN Center for Integrative Medical Sciences (JP)
- Emory University (US)
- Corresponding author
- Mabbott, N A
- Venue
- Mucosal Immunology
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 6
- Issue
- 4
- Pages
- 666-677
- ISSN
- 1933-0219 (ISSN-L)
- PMC
- PMC3686595
- OpenAlex
- W2085355903
- Cited by
- 721
- References
- 118
- Citations by year
- 2026: 52 · 2025: 48 · 2024: 61 · 2023: 66 · 2022: 50 · 2021: 68 · 2020: 71 · 2019: 54 · 2018: 78 · 2017: 56 · 2016: 43 · 2015: 46 · 2014: 22 · 2013: 5
- FWCI
- 3.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Mucosal Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- National Institutes of Health
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council (BB/G003947/1, BB/F019726/1, BB/J014672/1, BBS/E/D/20231759, BB/J0004332/1, BB/K021257/1, BBS/E/D/20251968, BBS/E/D/20251967, JPA1797)
- Japan Society for the Promotion of Science (24249029)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK064730, DK-064730)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- M cells, Peyer's patches, intestinal epithelium, mucosal immunity, immune surveillance, host genes, aging, mucosal vaccines, antigen targeting
- MeSH terms
- Age Factors, Animals, Antigens, Antigens, Surface, Cell Communication, Cell Differentiation, Humans, Intestinal Mucosa, Peyer's Patches, Stem Cells, Transcription Factors, Monitoring, Immunologic, Receptors, G-Protein-Coupled, RANK Ligand, Host-Pathogen Interactions
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