Specialized epithelial cells in Peyer's patches and other gut-associated lymphoid tissue (GALT) that sample luminal antigens via transcytosis and deliver them to underlying immune cells (dendritic cells, macrophages, T cells, B cells). M cells are critical for establishing oral tolerance and detecting pathogens but can also be exploited by pathogens for invasion.
M cells differ from enterocytes structurally and functionally: (1) Morphology—lack dense microvilli ('M' stands for microfold), creating thin apical surface facilitating antigen uptake, (2) Transcytosis—actively sample particles, bacteria, proteins from lumen via endocytosis/phagocytosis and transport them across epithelium in vesicles to basolateral 'pocket' containing immune cells, (3) Antigen presentation—delivered antigens are captured by dendritic cells which migrate to mesenteric lymph nodes to present to T cells, initiating either tolerance (default pathway via Tregs) or immune response (if danger signals present), (4) No secretory IgA production—M cells themselves don't contribute to mucosal immunity, they facilitate antigen surveillance. M cells express specific receptors (β1 integrin, GP2) allowing pathogen attachment. Pathogens like Salmonella, Yersinia, Shigella specifically target M cells for invasion.
M cells represent a controlled 'window' in the intestinal barrier, essential for immune education and tolerance but also a vulnerability. Understanding M cell function explains: (1) How oral tolerance develops—constant sampling of food antigens presented to dendritic cells in tolerogenic environment creates Tregs, (2) Why some infections begin in Peyer's patches—pathogens evolved to exploit M cell transcytosis, (3) Vaccine strategy—oral vaccines target M cells for antigen delivery, (4) Barrier dysfunction—when inflammation disrupts M cell regulation or increases M cell number, excessive antigen translocation can occur. In cPNI, supporting healthy M cell function means: maintaining normal gut microbiome (which regulates M cell development), reducing intestinal inflammation, ensuring adequate Treg development.