BREATHE

A Multidisciplinary Collaborative on Air Quality & Health Research

M Cells and Immune Surveillance

The immune system defends against infectious organisms such as bacteria and viruses, but the defense depends on active surveillance to detect and identify invading organisms. Although intestine and lungs are “inside” the body, they are topologically “outside” - exposed to external environment at the intestinal epithelium and airways. In fact, about 70% of disease-causing infectious microbes enter the body through these surfaces, so surveillance is important here.  

That is where M cells come in. They are a specialized subset of epithelial cells in the lining of the intestine and airways, mainly found above organized immune tissue. They are particularly adept at capturing particles such as bacteria and viruses at the epithelial surface, and carrying them across the epithelial boundary to cells of the mucosal immune system.

This surveillance function is so important that we are finding epithelial cells with M cell-like properties in other tissues as well. 

Selected References

  1. Lo, D., Tynan, W., Dickerson, J., Mendy, J., Chang, H.-W., Scharf, M., Byrne, D., Brayden, D., Higgins, L., Evans, C., O’Mahony, D.J., Peptidoglycan recognition protein expression in mouse Peyer’s patch Follicle Associated Epithelium suggests functional specialization. Cell. Immunol. 224:8-16, 2003. (PMID: 14572796)
  2. Lo, D., Tynan, W., Dickerson, J., Scharf, M., Cooper, J., Byrne, D., Brayden, D., Higgins, L., Evans, C., and O’Mahony, D.J., Cell culture modeling of specialized tissue: Identification of genes expressed specifically by Follicle Associated Epithelium of Peyer’s Patch by expression profiling of Caco-2/Raji co-cultures. Intl. Immunol. 16:91-99, 2004. (PMID: 14688064)
  3. Wang, J., Lopez-Fraga M., Rynko, A., Lo, D.D. TNFR and LTbetaR agonists induce Follicle-Associated Epithelium and M cell specific genes in rat and human intestinal epithelial cells. Cytokine 47:69-76, 2009. (PMCID: PMC2756805)
  4. Rajapaksa, T.E., Stover-Hamer, M., Fernandez, X., Eckelhoefer, H., and Lo, D.D., Claudin-4-targeted protein incorporated into PLGA nanoparticles can mediate M cell targeted delivery. J. Controlled Release 142: 196-205 (ePub November 5, 2009), 2010. (PMCID: PMC2823968)
  5. Hsieh, E.H., Fernandez, X., Wang, J., Stover-Hamer, M., Calvillo, S., Croft, M., Kwon, B.S., and Lo, D.D., CD137 is required for M cell functional maturation. Am. J. Pathol. 177: 666-676 (ePub Jul 8), 2010. (PMCID: PMC2913358)
  6. Rajapaksa, T.E., Bennett, K., Hamer, M , Lytle, C., Rodgers, V.G.J., and Lo, D.D., Intranasal M cell uptake of nanoparticles is independently influenced by targeting ligands and solvent ionic strength. J. Biol Chem. 285:23739-46 (ePub May 28), 2010. (PMCID: PMC2911333)
  7. Wang, J., Gusti, V., Saraswati, A., and Lo, D. D., Convergent and divergent development among M cell lineages in mouse mucosal epithelium. J. Immunol. 187:5277-85, 2011. (PMCID: 3208058) Highlighted “In This Issue” (J. Immunol. 187;4925-4926, 2011)
  8. Woodward, K., Bennett, K., and Lo, D.D., Mucosal vaccine design and delivery. Annu. Rev. Biomed. Engr. 14:17-46, 2012. (PMID: 22524387)
  9. Lo, D.D., Ling, J., and Eckelhoefer, H.A., M cell targeting by a claudin 4 targeting peptide can enhance mucosal IgA responses. BMC Biotechnology. 12:7, 2012. (PMCID:3337280)
  10. Hsieh, E.-H., and Lo, D.D., Jagged1 and Notch1 help edit M cell patterning in Peyer’s patch follicle epithelium. Dev. Comp. Immunol. 37:306-12, 2012. (PMCID: PMC3374009)
  11. Bennett, K.M., Walker, S.L., and Lo, D.D., Epithelial microvilli establish an electrostatic barrier to microbial adhesion. Infect. Immun. 82: 2860-2871, 2014. (PMID: 24778113) Highlighted in “IAI Spotlight”
  12. Sakhon, O.S., Ross, B., Gusti, V., Pham, A.J., Vu, K., and Lo, D.D., M cell-derived vesicles suggest a unique pathway for trans-epithelial antigen delivery. Tissue Barriers 3:1-2 (e1004975), 2015. (PMID 25838974)
  13. Bennett, K.M., Parnell, E.A., Sanscartier, C., Parks, S., Chen, G., Nair, M.G., and Lo, D.D., Induction of colonic M cells during intestinal inflammation. Am. J. Pathol. 186:1166-79, 2016 (PMID 26948422).
  14. Parnell, E.A., Walch, E.M., Lo, D.D., Inducible colonic M cells are dependent on TNFR2 but not LTR, identifying distinct signaling requirements for constitutive versus inducible M cells. J. Crohn’s and Colitis 11:751-760, 2017. (PMID 27932454)
  15. Givony, T., Leshkowitz, D., Del Castillo, D., Nevo, S., Kadouri, N., Dassa, B., Gruper, Y., Khalaila, R., Ben-Nun, O., Gome, T., Dobes, J., Ben-Dor, S., Kedmi, M., Keren-Shaul, H., Heffner-Krausz, R., Porat,Z., Golani, O., Addadi, Y., Brenner, O., Lo, D.D., Goldfarb, Y., Abramson, J., Thymic microfold and endocrine cells regulate thymus homeostasis and self-tolerance. Nature, 2023. https://doi.org/10.1038/s41586-023-06512-8
  16. Del Castillo, D., Lo, D.D., Deciphering the M Cell Niche: Insights from Mouse Models on how Microfold Cells 'Know' Where They Are Needed. Frontiers in Immunology section Mucosal Immunology, Front. Immunol. 15:1400739, 2024. (doi: 10.3389/fimmu.2024.1400739)
  17. Yisrael Gayle, K., et al., Evidence for aerosolized environmental bacterial endotoxin as an environmental health hazard. MS ID#: MEDRXIV/2025/337178 doi: https://doi.org/10.1101/2025.10.02.25337178