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Intestinal epithelial cells (IECs) constitute the single-cell layer lining the gastrointestinal tract, functioning as both a physical barrier and a mediator of nutrient absorption and immune homeostasis (Mabbott et al., 2013, Nature Reviews Microbiology). M cells (Microfold cells) are a specialized subset of IECs found within the follicle-associated epithelium (FAE) overlying lymphoid follicles like Peyer's patches. The primary role of M cells is the surveillance of the intestinal lumen through the transcytosis of antigens and microorganisms to the underlying mucosal immune system (Neutra et al., 2001, Nature Reviews Immunology). In clinical contexts, these cells are not traditional molecular targets but are critical sites for the delivery of oral vaccines and mucosal immunotherapies. Pathologically, M cells can be exploited by pathogens such as Salmonella and Prions as entry points, and dysfunction in the epithelial barrier is a hallmark of inflammatory bowel diseases (Hase et al., 2009, Nature). Furthermore, the differentiation of M cells is regulated by specific factors like the RANKL-RANK signaling pathway and the transcription factor Spi-B (Kanaya et al., 2012, Nature Immunology). Targeting these cells effectively requires understanding their unique surface markers, such as Glycoprotein 2, which facilitates the uptake of specific bacterial fimbriae.
M cells facilitate the transcytosis of luminal antigens and drug delivery vehicles across the epithelial barrier to the underlying gut-associated lymphoid tissue (GALT) to initiate an immune response (Mabbott et al., 2013, Nature Reviews Microbiology).
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