{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363670320433768192.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1038/nature08529"}},{"identifier":{"@type":"URI","@value":"http://www.nature.com/articles/nature08529.pdf"}},{"identifier":{"@type":"URI","@value":"http://www.nature.com/articles/nature08529"}},{"identifier":{"@type":"PMID","@value":"20353296"}}],"dc:title":[{"@value":"Uptake through glycoprotein 2 of FimH+ bacteria by M cells initiates mucosal immune response"}],"description":[{"notation":[{"@value":"The mucosal immune system forms the largest part of the entire immune system, containing about three-quarters of all lymphocytes and producing grams of secretory IgA daily to protect the mucosal surface from pathogens. To evoke the mucosal immune response, antigens on the mucosal surface must be transported across the epithelial barrier into organized lymphoid structures such as Peyer's patches. This function, called antigen transcytosis, is mediated by specialized epithelial M cells. The molecular mechanisms promoting this antigen uptake, however, are largely unknown. Here we report that glycoprotein 2 (GP2), specifically expressed on the apical plasma membrane of M cells among enterocytes, serves as a transcytotic receptor for mucosal antigens. Recombinant GP2 protein selectively bound a subset of commensal and pathogenic enterobacteria, including Escherichia coli and Salmonella enterica serovar Typhimurium (S. Typhimurium), by recognizing FimH, a component of type I pili on the bacterial outer membrane. Consistently, these bacteria were colocalized with endogenous GP2 on the apical plasma membrane as well as in cytoplasmic vesicles in M cells. Moreover, deficiency of bacterial FimH or host GP2 led to defects in transcytosis of type-I-piliated bacteria through M cells, resulting in an attenuation of antigen-specific immune responses in Peyer's patches. GP2 is therefore a previously unrecognized transcytotic receptor on M cells for type-I-piliated bacteria and is a prerequisite for the mucosal immune response to these bacteria. Given that M cells are considered a promising target for oral vaccination against various infectious diseases, the GP2-dependent transcytotic pathway could provide a new target for the development of M-cell-targeted mucosal vaccines."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1420845751159509760","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"20359714"},{"@type":"NRID","@value":"1000020359714"},{"@type":"NRID","@value":"9000405632435"},{"@type":"NRID","@value":"9000386354086"},{"@type":"NRID","@value":"9000409765066"},{"@type":"NRID","@value":"9000406183554"},{"@type":"NRID","@value":"9000018815885"},{"@type":"NRID","@value":"9000243571225"},{"@type":"NRID","@value":"9000254712363"},{"@type":"NRID","@value":"9000276440420"},{"@type":"NRID","@value":"9000019157200"},{"@type":"NRID","@value":"9000255959830"},{"@type":"NRID","@value":"9000010580984"},{"@type":"NRID","@value":"9000018282541"},{"@type":"NRID","@value":"9000413774109"},{"@type":"NRID","@value":"9000397866572"},{"@type":"NRID","@value":"9000411394713"},{"@type":"NRID","@value":"9000329003857"},{"@type":"NRID","@value":"9000254712495"},{"@type":"NRID","@value":"9000255959612"},{"@type":"NRID","@value":"9000297491577"},{"@type":"NRID","@value":"9000410160916"},{"@type":"NRID","@value":"9000414857062"},{"@type":"NRID","@value":"9000242076304"},{"@type":"NRID","@value":"9000283604234"},{"@type":"NRID","@value":"9000242744687"},{"@type":"NRID","@value":"9000402085158"},{"@type":"NRID","@value":"9000405713228"},{"@type":"NRID","@value":"9000254709325"},{"@type":"NRID","@value":"9000390425691"},{"@type":"NRID","@value":"9000356893399"},{"@type":"NRID","@value":"9000309578305"},{"@type":"NRID","@value":"9000384355569"},{"@type":"NRID","@value":"9000404135785"},{"@type":"NRID","@value":"9000262361434"},{"@type":"NRID","@value":"9000335193797"},{"@type":"NRID","@value":"9000255679793"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0103013"}],"foaf:name":[{"@value":"Koji Hase"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768206","@type":"Researcher","foaf:name":[{"@value":"Kazuya Kawano"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768202","@type":"Researcher","foaf:name":[{"@value":"Tomonori Nochi"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768196","@type":"Researcher","foaf:name":[{"@value":"Gemilson Soares Pontes"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768200","@type":"Researcher","foaf:name":[{"@value":"Shinji Fukuda"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768201","@type":"Researcher","foaf:name":[{"@value":"Masashi Ebisawa"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768212","@type":"Researcher","foaf:name":[{"@value":"Kazunori Kadokura"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768204","@type":"Researcher","foaf:name":[{"@value":"Toru Tobe"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768195","@type":"Researcher","foaf:name":[{"@value":"Yumiko Fujimura"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768210","@type":"Researcher","foaf:name":[{"@value":"Sayaka Kawano"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768194","@type":"Researcher","foaf:name":[{"@value":"Atsuko Yabashi"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768203","@type":"Researcher","foaf:name":[{"@value":"Satoshi Waguri"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768208","@type":"Researcher","foaf:name":[{"@value":"Gaku Nakato"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768209","@type":"Researcher","foaf:name":[{"@value":"Shunsuke Kimura"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768193","@type":"Researcher","foaf:name":[{"@value":"Takaya Murakami"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768207","@type":"Researcher","foaf:name":[{"@value":"Mitsutoshi Iimura"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768197","@type":"Researcher","foaf:name":[{"@value":"Kimiyo Hamura"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768211","@type":"Researcher","foaf:name":[{"@value":"Shin-Ichi Fukuoka"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768198","@type":"Researcher","foaf:name":[{"@value":"Anson W. Lowe"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768199","@type":"Researcher","foaf:name":[{"@value":"Kikuji Itoh"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768064","@type":"Researcher","foaf:name":[{"@value":"Hiroshi Kiyono"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320433768205","@type":"Researcher","foaf:name":[{"@value":"Hiroshi Ohno"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00280836"},{"@type":"EISSN","@value":"14764687"},{"@type":"PISSN","@value":"http://id.crossref.org/issn/14764687"}],"prism:publicationName":[{"@value":"Nature"}],"dc:publisher":[{"@value":"Springer Science and Business Media LLC"}],"prism:publicationDate":"2009-11","prism:volume":"462","prism:number":"7270","prism:startingPage":"226","prism:endingPage":"230"},"reviewed":"false","dc:rights":["http://www.springer.com/tdm"],"url":[{"@id":"http://www.nature.com/articles/nature08529.pdf"},{"@id":"http://www.nature.com/articles/nature08529"}],"createdAt":"2009-11-10","modifiedAt":"2023-05-27","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Salmonella%20typhimurium","dc:title":"Salmonella typhimurium"},{"@id":"https://cir.nii.ac.jp/all?q=GPI-Linked%20Proteins","dc:title":"GPI-Linked Proteins"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Line","dc:title":"Cell Line"},{"@id":"https://cir.nii.ac.jp/all?q=Substrate%20Specificity","dc:title":"Substrate Specificity"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Peyer's%20Patches","dc:title":"Peyer's Patches"},{"@id":"https://cir.nii.ac.jp/all?q=Escherichia%20coli","dc:title":"Escherichia coli"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Immunity,%20Mucosal","dc:title":"Immunity, Mucosal"},{"@id":"https://cir.nii.ac.jp/all?q=Glycoproteins","dc:title":"Glycoproteins"},{"@id":"https://cir.nii.ac.jp/all?q=Adhesins,%20Escherichia%20coli","dc:title":"Adhesins, Escherichia coli"},{"@id":"https://cir.nii.ac.jp/all?q=Antigens,%20Bacterial","dc:title":"Antigens, Bacterial"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Inbred%20BALB%20C","dc:title":"Mice, Inbred BALB C"},{"@id":"https://cir.nii.ac.jp/all?q=Membrane%20Glycoproteins","dc:title":"Membrane Glycoproteins"},{"@id":"https://cir.nii.ac.jp/all?q=Epithelial%20Cells","dc:title":"Epithelial Cells"},{"@id":"https://cir.nii.ac.jp/all?q=Intestines","dc:title":"Intestines"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Inbred%20C57BL","dc:title":"Mice, Inbred C57BL"},{"@id":"https://cir.nii.ac.jp/all?q=Fimbriae%20Proteins","dc:title":"Fimbriae Proteins"},{"@id":"https://cir.nii.ac.jp/all?q=HeLa%20Cells","dc:title":"HeLa Cells"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050306506455411840","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Visualization of the entire differentiation process of murine M cells : suppression of their maturation in cecal patches"},{"@value":"Visualization of the entire differentiation process of murine M cells: suppression of their maturation in caecal patches"}]},{"@id":"https://cir.nii.ac.jp/crid/1050586963913289344","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer’s 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maturation of M cells in the follicle-associated epithelium"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004233415430912","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Transcription factor Spi-B–dependent and –independent pathways for the development of Peyer's patch M cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004234612223104","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"A novel mucosal vaccine targeting Peyer’s patch M cells induces protective antigen-specific IgA responses"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004234947517056","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Osteoimmunology"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004235709930240","@type":"Article","resourceType":"学術雑誌論文(journal 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That is the question"}]},{"@id":"https://cir.nii.ac.jp/crid/1360022307169248640","@type":"Article","resourceType":"preprint","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Genome-wide association meta-analysis identifies novel\n                  <i>GP2</i>\n                  gene risk variants for pancreatic cancer in the Japanese population"}]},{"@id":"https://cir.nii.ac.jp/crid/1360283691777539200","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex"}]},{"@id":"https://cir.nii.ac.jp/crid/1360283691784146688","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Mice carrying a knock-in mutation of Aicda resulting in a defect in somatic hypermutation have impaired gut homeostasis and compromised mucosal 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article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Mucosal Immunosenescence in the Gastrointestinal Tract: A Mini-Review"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285704956020480","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Defining the Interaction of Human Soluble Lectin ZG16p and Mycobacterial Phosphatidylinositol Mannosides"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285705356604288","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"M Cell-Targeted Mucosal Vaccine Strategies"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285706223158656","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Cyclophilin A is a new M cell marker of bovine intestinal 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article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"IL-22BP dictates characteristics of Peyer’s patch follicle-associated epithelium for antigen uptake"}]},{"@id":"https://cir.nii.ac.jp/crid/1360298755637474048","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Levilactobacillus brevis surface layer protein B promotes liposome targeting to antigen-presenting cells in Peyer’s patches"}]},{"@id":"https://cir.nii.ac.jp/crid/1360302865531952768","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Glycoprotein 2 as a gut gate keeper for mucosal equilibrium between inflammation and immunity"}]},{"@id":"https://cir.nii.ac.jp/crid/1360565165772876800","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"GPI-anchor remodeling: Potential functions of GPI-anchors in intracellular trafficking and membrane dynamics"}]},{"@id":"https://cir.nii.ac.jp/crid/1360565166145549568","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"The mucosal immune system for vaccine development"}]},{"@id":"https://cir.nii.ac.jp/crid/1360565166749706112","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Microfold (M) cells: important immunosurveillance posts in the intestinal epithelium"}]},{"@id":"https://cir.nii.ac.jp/crid/1360565166757656320","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Botulinum toxin A complex exploits intestinal M cells to enter the host and exert neurotoxicity"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567180050287744","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Mucosal innate immune cells regulate both gut homeostasis and intestinal inflammation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567181144425344","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"M cell–targeting strategy enhances systemic and mucosal immune responses induced by oral administration of nuclease-producing L. lactis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567181199850752","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"RANKL regulates differentiation of microfold cells in mouse nasopharynx-associated lymphoid tissue (NALT)"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567181497832064","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Molecular insights into the 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