title: Differential regulation of CD103 (αE integrin) expression in human dendritic cells by retinoic acid and Toll-like receptor ligands.
abstract: CD103 (αE integrin) is an important dendritic cell (DC) marker that characterizes functionally distinct DC subsets in mice and humans. However, the mechanism by which CD103 expression is regulated in human DCs and the role of CD103 for DC function are not very well understood. Here, we show that retinoic acid (RA) treatment of human monocyte-derived DCs (MoDCs) increased the ability of the DCs to synthesize RA and induced MoDC expression of CD103 and β7 at the mRNA and protein level. In contrast, RA was unable to induce the expression of CD103 in primary human DCs isolated from the gastric mucosa. Inhibition of TGF-β signaling in MoDCs down-regulated RA-induced CD103 expression, indicating that TGF-β-dependent pathways contribute to the induction of CD103. Conversely, when RA-treated MoDCs were stimulated with liveHelicobacter pylori, commensal bacteria, LPS, or a TLR2 agonist, the RA-induced up-regulation of CD103 and β7 integrin expression was completely abrogated. To determine whether CD103 expression impacts DC priming of CD4+T cells, we next investigated the ability of CD103+and CD103─DCs to induce mucosal homing and T cell proliferation. Surprisingly, RA treatment of DCs enhanced both α4β7 expression and proliferation in cocultured T cells, but no difference was seen between RA-treated CD103+and CD103─DCs. In summary, our data demonstrate that RA, bacterial products, and the tissue environment all contribute to the regulation of CD103 on human DCs and that DC induction of mucosal homing in T cells is RA dependent but not CD103 dependent.
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA.
authors.forename: Mandi M
authors.initials: MM
authors.lastname: Roe
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Swain
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA.
authors.forename: T Andrew
authors.initials: TA
authors.lastname: Sebrell
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA.
authors.forename: Marisa A
authors.initials: MA
authors.lastname: Sewell
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA.
authors.forename: Madison M
authors.initials: MM
authors.lastname: Collins
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, Nevada, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Perrino
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; and.|VA Medical Center, Birmingham, Alabama, USA.
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Smith
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; and.
authors.forename: Lesley E
authors.initials: LE
authors.lastname: Smythies
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA; diane.bimczok@montana.edu.
authors.forename: Diane
authors.initials: D
authors.lastname: Bimczok
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D002454:Cell Differentiation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D005786:Gene Expression Regulation; D016480:Helicobacter pylori / Q000254:growth & development / Q000276:immunology; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics / Q000276:immunology*; D039641:Integrin beta Chains / Q000235:genetics / Q000276:immunology*; D016023:Integrins / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000235:genetics / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D014212:Tretinoin / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; D039641:Integrin beta Chains; D016023:Integrins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D016212:Transforming Growth Factor beta; C091367:alpha E integrins; C071777:integrin alpha4beta7; C091368:integrin beta7; D014212:Tretinoin
keywords: H. pylori; TGF-β; gastric DCs; retinoids; β7 integrin