{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:09:06Z","timestamp":1791616146119,"version":"4.3.4"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:00:00Z","timestamp":1320105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>M cells are specialized epithelial cells mediating immune surveillance of the mucosal lumen by transepithelial delivery of Ags to underlying dendritic cells (DC). At least three M cell phenotypes are known in the airways and intestine, but their developmental relationships are unclear. We used reporter transgenic mouse strains to follow the constitutive development of M cell subsets and their acute induction by cholera toxin (CT). M cells overlying intestinal Peyer\u2019s patches (PPs), isolated lymphoid follicles, and nasal-associated lymphoid tissue are induced by distinct settings, yet show convergent phenotypes, such as expression of a peptidoglycan recognition protein-S (PGRP-S) transgene reporter. By contrast, though PP, isolated lymphoid follicle, and villous M cells are all derived from intestinal crypt stem cells, their phenotypes were clearly distinct; for example, PP M cells frequently appeared to form M cell-DC functional units, whereas villous M cells did not consistently engage underlying DC. B lymphocytes are critical to M cell function by forming a basolateral pocket and possible signaling through CD137; however, initial commitment to all M cell lineages is B lymphocyte and CD137 independent. CT causes induction of new M cells in the airway and intestine without cell division, suggesting transdifferentiation from mature epithelial cells. In contrast with intestinal PP M cells, CT-induced nasal-associated lymphoid tissue M cells appear to be generated from ciliated Foxj1+PGRP-S+ cells, indicative of a possible precommitted progenitor. In summary, constitutive and inducible differentiation of M cells is toward strictly defined context-dependent phenotypes, suggesting specialized roles in surveillance of mucosal Ags.<\/jats:p>","DOI":"10.4049\/jimmunol.1102077","type":"journal-article","created":{"date-parts":[[2011,10,8]],"date-time":"2011-10-08T00:27:33Z","timestamp":1318033653000},"page":"5277-5285","source":"Crossref","is-referenced-by-count":82,"title":["Convergent and Divergent Development among M Cell Lineages in Mouse Mucosal Epithelium"],"prefix":"10.1093","volume":"187","author":[{"given":"Jing","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Biomedical Sciences, University of California Riverside , Riverside, CA 92521"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Gusti","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, University of California Riverside , Riverside, CA 92521"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Saraswati","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, University of California Riverside , Riverside, CA 92521"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D","family":"Lo","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, University of California Riverside , Riverside, CA 92521"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,11,15]]},"reference":[{"key":"2025032410455195200_r1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1146\/annurev.cellbio.16.1.301","article-title":"Epithelial M cells: differentiation and function","volume":"16","author":"Kraehenbuhl","year":"2000","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2025032410455195200_r2","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0092-8674(00)80106-3","article-title":"Epithelial M cells: gateways for mucosal infection and immunization","volume":"86","author":"Neutra","year":"1996","journal-title":"Cell"},{"key":"2025032410455195200_r3","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1146\/annurev.immunol.14.1.275","article-title":"Antigen sampling across epithelial barriers and induction of mucosal immune responses","volume":"14","author":"Neutra","year":"1996","journal-title":"Annu. Rev. Immunol."},{"key":"2025032410455195200_r4","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0016-5085(74)80102-2","article-title":"Epithelial cell specialization within human Peyer\u2019s patches: an ultrastructural study of intestinal lymphoid follicles","volume":"66","author":"Owen","year":"1974","journal-title":"Gastroenterology"},{"key":"2025032410455195200_r5","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/BF00218901","article-title":"An immunohistochemical study on the postnatal development of rat nasal-associated lymphoid tissue (NALT)","volume":"256","author":"Hameleers","year":"1989","journal-title":"Cell Tissue Res."},{"key":"2025032410455195200_r6","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/jlb.35.4.397","article-title":"Demonstration of M cells in the specialized follicle-associated epithelium overlying isolated lymphoid follicles in the gut","volume":"35","author":"Rosner","year":"1984","journal-title":"J. Leukoc. Biol."},{"key":"2025032410455195200_r7","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/BF00271042","article-title":"Vimentin antibodies stain membranous epithelial cells in the rabbit bronchus-associated lymphoid tissue (BALT)","volume":"98","author":"Gebert","year":"1992","journal-title":"Histochemistry"},{"key":"2025032410455195200_r8","doi-asserted-by":"crossref","first-page":"6110","DOI":"10.1073\/pnas.0400969101","article-title":"Intestinal villous M cells: an antigen entry site in the mucosal epithelium","volume":"101","author":"Jang","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032410455195200_r9","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/S1074-7613(02)00395-3","article-title":"CD4+CD3- cells induce Peyer\u2019s patch development: role of alpha4beta1 integrin activation by CXCR5","volume":"17","author":"Finke","year":"2002","journal-title":"Immunity"},{"key":"2025032410455195200_r10","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.cyto.2009.05.001","article-title":"TNFR and LTbetaR agonists induce follicle-associated epithelium and M cell specific genes in rat and human intestinal epithelial cells","volume":"47","author":"Wang","year":"2009","journal-title":"Cytokine"},{"key":"2025032410455195200_r11","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1093\/oxfordjournals.bmb.a070561","article-title":"The turnover of the epithelium of the small intestine","volume":"23","author":"Creamer","year":"1967","journal-title":"Br. Med. Bull."},{"key":"2025032410455195200_r12","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/S0016-5085(24)05125-4","article-title":"Structure, distribution, and origin of M cells in Peyer\u2019s patches of mouse ileum","volume":"86","author":"Bye","year":"1984","journal-title":"Gastroenterology"},{"key":"2025032410455195200_r13","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1177\/002215549704501003","article-title":"Glycoconjugate expression defines the origin and differentiation pathway of intestinal M-cells","volume":"45","author":"Gebert","year":"1997","journal-title":"J. Histochem. Cytochem."},{"key":"2025032410455195200_r14","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/S0002-9440(10)65410-7","article-title":"The development of M cells in Peyer\u2019s patches is restricted to specialized dome-associated crypts","volume":"154","author":"Gebert","year":"1999","journal-title":"Am. J. Pathol."},{"key":"2025032410455195200_r15","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1126\/science.277.5328.949","article-title":"Conversion by Peyer\u2019s patch lymphocytes of human enterocytes into M cells that transport bacteria","volume":"277","author":"Kern\u00e9is","year":"1997","journal-title":"Science"},{"key":"2025032410455195200_r16","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1096\/fasebj.13.6.611","article-title":"Up-regulation of microsphere transport across the follicle-associated epithelium of Peyer\u2019s patch by exposure to Streptococcus pneumoniae R36a","volume":"13","author":"Meynell","year":"1999","journal-title":"FASEB J."},{"key":"2025032410455195200_r17","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1002\/(SICI)1096-9896(199611)180:3<326::AID-PATH656>3.0.CO;2-6","article-title":"Modifications of the follicle-associated epithelium by short-term exposure to a non-intestinal bacterium","volume":"180","author":"Borghesi","year":"1996","journal-title":"J. Pathol."},{"key":"2025032410455195200_r18","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.bbrc.2010.12.067","article-title":"Distinct fucosylation of M cells and epithelial cells by Fut1 and Fut2, respectively, in response to intestinal environmental stress","volume":"404","author":"Terahara","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2025032410455195200_r19","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.0105-2896.2005.00281.x","article-title":"Development of intestinal M cells","volume":"206","author":"Mach","year":"2005","journal-title":"Immunol. Rev."},{"key":"2025032410455195200_r20","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1126\/science.286.5446.1965","article-title":"Organogenic role of B lymphocytes in mucosal immunity","volume":"286","author":"Golovkina","year":"1999","journal-title":"Science"},{"key":"2025032410455195200_r21","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/S1286-4579(00)01266-1","article-title":"Molecular studies of the intestinal mucosal barrier physiopathology using cocultures of epithelial and immune cells: a technical update","volume":"2","author":"Kern\u00e9is","year":"2000","journal-title":"Microbes Infect."},{"key":"2025032410455195200_r22","doi-asserted-by":"crossref","first-page":"666","DOI":"10.2353\/ajpath.2010.090811","article-title":"CD137 is required for M cell functional maturation but not lineage commitment","volume":"177","author":"Hsieh","year":"2010","journal-title":"Am. J. Pathol."},{"key":"2025032410455195200_r23","doi-asserted-by":"crossref","first-page":"L231","DOI":"10.1152\/ajplung.90209.2008","article-title":"Ciliated epithelial cell lifespan in the mouse trachea and lung","volume":"295","author":"Rawlins","year":"2008","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"2025032410455195200_r24","doi-asserted-by":"crossref","first-page":"12771","DOI":"10.1073\/pnas.0906850106","article-title":"Basal cells as stem cells of the mouse trachea and human airway epithelium","volume":"106","author":"Rock","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032410455195200_r25","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1073\/pnas.0610770104","article-title":"Lung development and repair: contribution of the ciliated lineage","volume":"104","author":"Rawlins","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032410455195200_r26","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/S1525-0016(03)00221-1","article-title":"Targeting expression of a transgene to the airway surface epithelium using a ciliated cell-specific promoter","volume":"8","author":"Ostrowski","year":"2003","journal-title":"Mol. Ther."},{"key":"2025032410455195200_r27","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/S0008-8749(03)00155-2","article-title":"Peptidoglycan recognition protein expression in mouse Peyer\u2019s Patch follicle associated epithelium suggests functional specialization","volume":"224","author":"Lo","year":"2003","journal-title":"Cell. Immunol."},{"key":"2025032410455195200_r28","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1182\/blood-2005-02-0530","article-title":"Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity","volume":"106","author":"Cho","year":"2005","journal-title":"Blood"},{"key":"2025032410455195200_r29","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.molimm.2003.10.011","article-title":"Peptidoglycan recognition proteins (PGRPs)","volume":"40","author":"Dziarski","year":"2004","journal-title":"Mol. Immunol."},{"key":"2025032410455195200_r30","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1177\/1753425910366059","article-title":"Review: mammalian peptidoglycan recognition proteins (PGRPs) in innate immunity","volume":"16","author":"Dziarski","year":"2010","journal-title":"Innate Immun."},{"key":"2025032410455195200_r31","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/nature08529","article-title":"Uptake through glycoprotein 2 of FimH(+) bacteria by M cells initiates mucosal immune response","volume":"462","author":"Hase","year":"2009","journal-title":"Nature"},{"key":"2025032410455195200_r32","doi-asserted-by":"crossref","first-page":"7840","DOI":"10.4049\/jimmunol.180.12.7840","article-title":"Comprehensive gene expression profiling of Peyer\u2019s patch M cells, villous M-like cells, and intestinal epithelial cells","volume":"180","author":"Terahara","year":"2008","journal-title":"J. Immunol."},{"key":"2025032410455195200_r33","doi-asserted-by":"crossref","first-page":"4106","DOI":"10.1128\/MCB.20.11.4106-4114.2000","article-title":"Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion","volume":"20","author":"Jung","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"2025032410455195200_r34","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1086\/591056","article-title":"Effects of flagellin on the functions of follicle-associated epithelium","volume":"198","author":"Chabot","year":"2008","journal-title":"J. Infect. Dis."},{"key":"2025032410455195200_r35","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0002-9440(10)63097-0","article-title":"Antigen transport into Peyer\u2019s patches: increased uptake by constant numbers of M cells","volume":"164","author":"Gebert","year":"2004","journal-title":"Am. J. Pathol."},{"key":"2025032410455195200_r36","doi-asserted-by":"crossref","first-page":"5738","DOI":"10.4049\/jimmunol.0901563","article-title":"RANKL is necessary and sufficient to initiate development of antigen-sampling M cells in the intestinal epithelium","volume":"183","author":"Knoop","year":"2009","journal-title":"J. Immunol."},{"key":"2025032410455195200_r37","doi-asserted-by":"crossref","first-page":"6803","DOI":"10.4049\/jimmunol.174.11.6803","article-title":"Enhanced CD4 T cell responsiveness in the absence of 4-1BB","volume":"174","author":"Lee","year":"2005","journal-title":"J. Immunol."},{"key":"2025032410455195200_r38","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/j.0105-2896.2005.00282.x","article-title":"Organizing a mucosal defense","volume":"206","author":"Newberry","year":"2005","journal-title":"Immunol. Rev."},{"key":"2025032410455195200_r39","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.2353\/ajpath.2007.060817","article-title":"CC chemokine receptor 6 expression by B lymphocytes is essential for the development of isolated lymphoid follicles","volume":"170","author":"McDonald","year":"2007","journal-title":"Am. J. Pathol."},{"key":"2025032410455195200_r40","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/j.1365-2249.2010.04103.x","article-title":"CCR6 identifies lymphoid tissue inducer cells within cryptopatches","volume":"160","author":"L\u00fcgering","year":"2010","journal-title":"Clin. Exp. Immunol."},{"key":"2025032410455195200_r41","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.immuni.2008.05.014","article-title":"Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut","volume":"29","author":"Tsuji","year":"2008","journal-title":"Immunity"},{"key":"2025032410455195200_r42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-4933-8-1","article-title":"Aging impacts isolated lymphoid follicle development and function","volume":"8","author":"McDonald","year":"2011","journal-title":"Immun. Ageing"},{"key":"2025032410455195200_r43","doi-asserted-by":"crossref","first-page":"L650","DOI":"10.1152\/ajplung.00170.2003","article-title":"Role of f-box factor foxj1 in differentiation of ciliated airway epithelial cells","volume":"286","author":"You","year":"2004","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"2025032410455195200_r44","doi-asserted-by":"crossref","first-page":"4253","DOI":"10.4049\/jimmunol.0903794","article-title":"The airway antigen sampling system: respiratory M cells as an alternative gateway for inhaled antigens","volume":"186","author":"Kim","year":"2011","journal-title":"J. Immunol."},{"key":"2025032410455195200_r45","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1084\/jem.134.1.188","article-title":"Peyer\u2019s patches: an enriched source of precursors for IgA-producing immunocytes in the rabbit","volume":"134","author":"Craig","year":"1971","journal-title":"J. Exp. Med."},{"key":"2025032410455195200_r46","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1084\/jem.148.5.1146","article-title":"The origin and antigen-dependent distribution of IgA-containing cells in the intestine","volume":"148","author":"Husband","year":"1978","journal-title":"J. Exp. Med."},{"key":"2025032410455195200_r47","doi-asserted-by":"crossref","first-page":"19658","DOI":"10.1074\/jbc.M200659200","article-title":"Isolation, characterization, and antimicrobial properties of bovine oligosaccharide-binding protein. A microbicidal granule protein of eosinophils and neutrophils","volume":"277","author":"Tydell","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2025032410455195200_r48","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.4049\/jimmunol.176.2.1154","article-title":"Bovine peptidoglycan recognition protein-S: antimicrobial activity, localization, secretion, and binding properties","volume":"176","author":"Tydell","year":"2006","journal-title":"J. Immunol."},{"key":"2025032410455195200_r49","doi-asserted-by":"crossref","first-page":"4275","DOI":"10.4049\/jimmunol.176.7.4275","article-title":"TLRs regulate the gatekeeping functions of the intestinal follicle-associated epithelium","volume":"176","author":"Chabot","year":"2006","journal-title":"J. Immunol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/187\/10\/5277\/61605134\/1102077.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/187\/10\/5277\/61605134\/1102077.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T02:03:47Z","timestamp":1743127427000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/187\/10\/5277\/7977184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11]]},"references-count":49,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2011,11,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1102077","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,11]]},"published":{"date-parts":[[2011,11]]}}}