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dc.contributor.authorSwain, Steve
dc.contributor.authorRoe, Mandi M.
dc.contributor.authorSebrell, T. Andrew
dc.contributor.authorSidar, Barkan
dc.contributor.authorDankoff, Jennifer
dc.contributor.authorVanAusdol, Rachel
dc.contributor.authorSmythies, Lesley E.
dc.contributor.authorSmith, Phillip D.
dc.contributor.authorBimczok, Diane
dc.date.accessioned2019-01-11T18:05:41Z
dc.date.available2019-01-11T18:05:41Z
dc.date.issued2018-12
dc.identifier.citationSwain, Steve, Mandi M. Roe, Thomas A. Sebrell, Barkan Sidar, Jennifer Dankoff, Rachel VanAusdol, Lesley E. Smythies, Phillip D. Smith, and Diane Bimczok. “CD103 (αE Integrin) Undergoes Endosomal Trafficking in Human Dendritic Cells, but Does Not Mediate Epithelial Adhesion.” Frontiers in Immunology 9 (December 21, 2018). doi:10.3389/fimmu.2018.02989.en_US
dc.identifier.issn1664-3224
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/15133
dc.description.abstractDendritic cell (DC) expression of CD103, the α subunit of αEβ7 integrin, is thought to enable DC interactions with E-cadherin-expressing gastrointestinal epithelia for improved mucosal immunosurveillance. In the stomach, efficient DC surveillance of the epithelial barrier is crucial for the induction of immune responses to H. pylori, the causative agent of peptic ulcers and gastric cancer. However, gastric DCs express only low levels of surface CD103, as we previously showed. We here tested the hypothesis that intracellular pools of CD103 in human gastric DCs can be redistributed to the cell surface for engagement of epithelial cell-expressed E-cadherin to promote DC-epithelial cell adhesion. In support of our hypothesis, immunofluorescence analysis of tissue sections showed that CD103+ gastric DCs were preferentially localized within the gastric epithelial layer. Flow cytometry and imaging cytometry revealed that human gastric DCs expressed intracellular CD103, corroborating our previous findings in monocyte-derived DCs (MoDCs). Using confocal microscopy, we show that CD103 was present in endosomal compartments, where CD103 partially co-localized with clathrin, early endosome antigen-1 and Rab11, suggesting that CD103 undergoes endosomal trafficking similar to β1 integrins. Dynamic expression of CD103 on human MoDCs was confirmed by internalization assay. To analyze whether DC-expressed CD103 promotes adhesion to E-cadherin, we performed adhesion and spreading assays on E-cadherin-coated glass slides. In MoDCs generated in the presence of retinoic acid, which express increased CD103, intracellular CD103 significantly redistributed toward the E-cadherin-coated glass surface. However, DCs spreading and adhesion did not differ between E-cadherin-coated slides and slides coated with serum alone. In adhesion assays using E-cadherin-positive HT-29 cells, DC binding was significantly improved by addition of Mn2+ and decreased in the presence of EGTA, consistent with the dependence of integrin-based interactions on divalent cations. However, retinoic acid failed to increase DC adhesion, and a CD103 neutralizing antibody was unable to inhibit DC binding to the E-cadherin positive cells. In contrast, a blocking antibody to DC-expressed E-cadherin significantly reduced DC binding to the epithelium. Overall, these data indicate that CD103 engages in DC-epithelial cell interactions upon contact with epithelial E-cadherin, but is not a major driver of DC adhesion to gastrointestinal epithelia.en_US
dc.description.sponsorshipNational Institutes of Health grants K01 DK097144 & R03 DK107960; Montana State University; National Institutes of Health IDeA Program grant GM110732; M. J. Murdock Charitable Trust 2016028:MNL:8/25/2016en_US
dc.language.isoenen_US
dc.rightsCC BY, This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcodeen_US
dc.titleCD103 (aE integrin) undergoes endosomal trafficking in human dendritic cells, but does not mediate epithelial adhesionen_US
dc.typeArticleen_US
mus.citation.journaltitleFrontiers in Immunologyen_US
mus.citation.volume9en_US
mus.identifier.categoryHealth & Medical Sciencesen_US
mus.identifier.doi10.3389/fimmu.2018.02989en_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.data.thumbpage7en_US


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CC BY, This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.
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