title: Lost therapeutic potential of monocyte-derived dendritic cells through lost tissue homing: stable restoration of gut specificity with retinoic acid.
abstract: Human monocyte-derived dendritic cells (DC) (MoDC) are utilized for immunotherapy. However, in-vitro immunological effects are often not mirrored in vivo. We studied the tissue-homing potential of MoDC. Circulating monocytes and DC expressed different tissue-homing markers and, during in-vitro development of MoDC, homing marker expression was lost resulting in a 'homeless' phenotype. Retinoic acid (RA) induced gut-homing markers (β7 and CCR9) and a regulatory phenotype and function [decreased human leucocyte antigen D-related (HLA-DR) and increased ILT3 and fluorescein isothiocyanate (FITC-dextran uptake) in MoDC]. RA-MoDC were less stimulatory and primed conditioned T cells with a gut-homing profile (β7(+)CLA(-)). Unlike the normal intestinal microenvironment, that from inflamed colon of ulcerative colitis (UC) patients did not induce regulatory properties in MoDC. However, RA-MoDC maintained their regulatory gut-specific properties even in the presence of UC microenvironment. Therefore, MoDC may be ineffectual for immunotherapy because they lack tissue-homing and tissue-imprinting specificity. However, MoDC rehabilitation with gut-homing potential by RA could be useful in promoting immunotherapy in pathologies such as UC.
authors.affiliation: Antigen Presentation Research Group, Imperial College London, Northwick Park & St Mark's Campus, UK.
authors.forename: D
authors.initials: D
authors.lastname: Bernardo
authors.forename: E R
authors.initials: ER
authors.lastname: Mann
authors.forename: H O
authors.initials: HO
authors.lastname: Al-Hassi
authors.forename: N R
authors.initials: NR
authors.lastname: English
authors.forename: R
authors.initials: R
authors.lastname: Man
authors.forename: G H
authors.initials: GH
authors.lastname: Lee
authors.forename: E
authors.initials: E
authors.lastname: Ronde
authors.forename: J
authors.initials: J
authors.lastname: Landy
authors.forename: S T C
authors.initials: ST
authors.lastname: Peake
authors.forename: A L
authors.initials: AL
authors.lastname: Hart
authors.forename: S C
authors.initials: SC
authors.lastname: Knight
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009928:Organ Specificity / Q000187:drug effects / Q000276:immunology; D054388:Receptors, CCR / Q000096:biosynthesis; D054400:Receptors, CCR7 / Q000096:biosynthesis; D014212:Tretinoin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; C119309:CC chemokine receptor 9; C515370:CCR7 protein, human; D054388:Receptors, CCR; D054400:Receptors, CCR7; D014212:Tretinoin
keywords: dendritic cell; homing markers; immunotherapy; retinoic acid; ulcerative colitis