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dc.contributor.authorSebrell, Thomas A.
dc.contributor.authorHashimi, Marziah
dc.contributor.authorSidar, Barkan
dc.contributor.authorWilkinson, Royce A.
dc.contributor.authorKirpotina, Liliya
dc.contributor.authorQuinn, Mark T.
dc.contributor.authorMalkoc, Zeynep
dc.contributor.authorTaylor, Paul J.
dc.contributor.authorWilking, James N.
dc.contributor.authorBimczok, Diane
dc.date.accessioned2019-07-31T19:02:50Z
dc.date.available2019-07-31T19:02:50Z
dc.date.issued2019-03
dc.identifier.citationSebrell, Thomas A., Marziah Hashimi, Barkan Sidar, Royce A. Wilkinson, Liliya Kirpotina, Mark T. Quinn, Zeynep Malkoç, Paul J. Taylor, James N. Wilking, and Diane Bimczok. “A Novel Gastric Spheroid Co-Culture Model Reveals Chemokine-Dependent Recruitment of Human Dendritic Cells to the Gastric Epithelium.” Cellular and Molecular Gastroenterology and Hepatology 8, no. 1 (2019): 157–171.e3. doi:10.1016/j.jcmgh.2019.02.010.en_US
dc.identifier.issn2352-345X
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/15629
dc.description.abstractBackground & Aims Gastric dendritic cells (DCs) control the adaptive response to infection with Helicobacter pylori, a major risk factor for peptic ulcer disease and gastric cancer. We hypothesize that DC interactions with the gastric epithelium position gastric DCs for uptake of luminal H pylori and promote DC responses to epithelial-derived mediators. The aim of this study was to determine whether the gastric epithelium actively recruits DCs using a novel co-culture model of human gastric epithelial spheroids and monocyte-derived DCs. Methods Spheroid cultures of primary gastric epithelial cells were infected with H pylori by microinjection. Co-cultures were established by adding human monocyte-derived DCs to the spheroid cultures and were analyzed for DC recruitment and antigen uptake by confocal microscopy. Protein array, gene expression polymerase chain reaction array, and chemotaxis assays were used to identify epithelial-derived chemotactic factors that attract DCs. Data from the co-culture model were confirmed using human gastric tissue samples. Results Human monocyte-derived DCs co-cultured with gastric spheroids spontaneously migrated to the gastric epithelium, established tight interactions with the epithelial cells, and phagocytosed luminally applied H pylori. DC recruitment was increased upon H pylori infection of the spheroids and involved the activity of multiple chemokines including CXCL1, CXCL16, CXCL17, and CCL20. Enhanced chemokine expression and DC recruitment to the gastric epithelium also was observed in H pylori–infected human gastric tissue samples. Conclusions Our results indicate that the gastric epithelium actively recruits DCs for immunosurveillance and pathogen sampling through chemokine-dependent mechanisms, with increased recruitment upon active H pylori infection.en_US
dc.description.sponsorshipNational Institutes of Health (R03 DK107960P30 GM110732R44 OD012083K01 DK097144); National Science Foundation (DMR-1455247); Montana University System Research Initiative (51040-MUSRI2015-03)en_US
dc.rightsCC BY-NC-ND: This license is the most restrictive of our six main licenses, only allowing you to download this work and share it with others as long as you credit the original creator, but you can’t change the work in any way or use it commercially.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/legalcodeen_US
dc.titleA Novel Gastric Spheroid Co-culture Model Reveals Chemokine-Dependent Recruitment of Human Dendritic Cells to the Gastric Epitheliumen_US
dc.typeArticleen_US
mus.citation.extentfirstpage151en_US
mus.citation.extentlastpage171en_US
mus.citation.issue1en_US
mus.citation.journaltitleCellular and Molecular Gastroenterology and Hepatologyen_US
mus.citation.volume8en_US
mus.identifier.doi10.1016/j.jcmgh.2019.02.010en_US
mus.relation.collegeCollege of Agricultureen_US
mus.relation.collegeCollege of Engineeringen_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentCenter for Biofilm Engineering.en_US
mus.relation.departmentChemical & Biological Engineering.en_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.data.thumbpage2en_US
mus.contributor.orcidQuinn, Mark T.|0000-0001-8114-5073en_US


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CC BY-NC-ND: This license is the most restrictive of our six main licenses, only allowing you to download this work and share it with others as long as you credit the original creator, but you can’t change the work in any way or use it commercially.
Except where otherwise noted, this item's license is described as CC BY-NC-ND: This license is the most restrictive of our six main licenses, only allowing you to download this work and share it with others as long as you credit the original creator, but you can’t change the work in any way or use it commercially.