title: Visualization of the entire differentiation process of murine M cells: suppression of their maturation in cecal patches.
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.
authors.affiliation: 1] Laboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan [2] Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Laboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamakami-Kimura
authors.affiliation: 1] Laboratory for Immune Regulation, Graduate School of Medicine, Chiba University, Chiba, Japan [2] Division of Mucosal Barriology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Obata
authors.affiliation: 1] Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, Japan [2] Division of Mucosal Barriology, Institute of Medical Science, University of Tokyo, Tokyo, Japan [3] PRESTO, Japan Science and Technology Agency, Tokyo, Japan [4] Department of Biochemistry, Faculty of Pharmacy, Keio University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hase
authors.affiliation: Department of Veterinary Physiology, School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kitamura
authors.affiliation: 1] Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, Japan [2] Division of Immunobiology, Department of Supramolecular Biology, Graduate School of Nanobioscience, Yokohama City University, Yokohama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ohno
authors.affiliation: Laboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iwanaga
mesh_terms: D000818:Animals; D002432:Cecum / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D002454:Cell Differentiation; D019070:Cell Lineage / Q000276:immunology; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000276:immunology; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D053245:RANK Ligand / Q000235:genetics / Q000276:immunology; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D051841:Transcription Factor RelB / Q000235:genetics / Q000276:immunology; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000276:immunology
chemical_list: C095218:Ccl9 protein, mouse; D019742:Chemokines, CC; D016207:Cytokines; D058851:GPI-Linked Proteins; C495998:Gp2 protein, mouse; C545682:M-sec protein, mouse; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B; C113582:Pglyrp1 protein, mouse; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C497594:Relb protein, mouse; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D048069:Tumor Necrosis Factors; D051841:Transcription Factor RelB