Abstract
The microfold (M) cell residing in the follicle-associated epithelium is a specialized epithelial cell that initiates mucosal immune responses by sampling luminal antigens. The differentiation process of M cells remains unclear due to limitations of analytical methods. Here we found that M cells were classified into two functionally different subtypes based on the expression of Glycoprotein 2 (GP2) by newly developed image cytometric analysis. GP2-high M cells actively took up luminal microbeads, whereas GP2-negative or low cells scarcely ingested them, even though both subsets equally expressed the other M-cell signature genes, suggesting that GP2-high M cells represent functionally mature M cells. Further, the GP2-high mature M cells were abundant in Peyer's patch but sparse in the cecal patch: this was most likely due to a decrease in the nuclear translocation of RelB, a downstream transcription factor for the receptor activator of nuclear factor-κB signaling. Given that murine cecum contains a protrusion of beneficial commensals, the restriction of M-cell activity might contribute to preventing the onset of any excessive immune response to the commensals through decelerating the M-cell-dependent uptake of microorganisms.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cecum / cytology
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Cecum / immunology
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Cecum / microbiology
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Cell Differentiation
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Cell Lineage / immunology
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Chemokines, CC / genetics
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Chemokines, CC / immunology
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Cytokines / genetics
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Cytokines / immunology
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Epithelial Cells / cytology
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Epithelial Cells / immunology
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Epithelial Cells / microbiology
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GPI-Linked Proteins / genetics
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GPI-Linked Proteins / immunology
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Gene Expression Regulation
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Immunity, Mucosal*
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Intestinal Mucosa / cytology
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Intestinal Mucosa / immunology
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Intestinal Mucosa / microbiology
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Macrophage Inflammatory Proteins / genetics
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Macrophage Inflammatory Proteins / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Microbiota / immunology
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Microscopy, Confocal
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NF-kappa B / genetics
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NF-kappa B / immunology
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Peyer's Patches / cytology
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Peyer's Patches / immunology
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Peyer's Patches / microbiology
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Phagocytosis / genetics
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Phagocytosis / immunology
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RANK Ligand / genetics
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RANK Ligand / immunology
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Receptor Activator of Nuclear Factor-kappa B / genetics
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Receptor Activator of Nuclear Factor-kappa B / immunology
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Signal Transduction
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Transcription Factor RelB / genetics
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Transcription Factor RelB / immunology
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Tumor Necrosis Factors / genetics
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Tumor Necrosis Factors / immunology
Substances
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Ccl9 protein, mouse
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Chemokines, CC
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Cytokines
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GPI-Linked Proteins
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Gp2 protein, mouse
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M-sec protein, mouse
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Macrophage Inflammatory Proteins
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NF-kappa B
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Pglyrp1 protein, mouse
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RANK Ligand
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Receptor Activator of Nuclear Factor-kappa B
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Relb protein, mouse
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Tnfrsf11a protein, mouse
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Tnfsf11 protein, mouse
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Tumor Necrosis Factors
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Transcription Factor RelB