title: Cancer-associated epithelial cell adhesion molecule (EpCAM; CD326) enables epidermal Langerhans cell motility and migration in vivo.
abstract: After activation, Langerhans cells (LC), a distinct subpopulation of epidermis-resident dendritic cells, migrate from skin to lymph nodes where they regulate the magnitude and quality of immune responses initiated by epicutaneously applied antigens. Modulation of LC-keratinocyte adhesion is likely to be central to regulation of LC migration. LC express high levels of epithelial cell adhesion molecule (EpCAM; CD326), a cell-surface protein that is characteristic of some epithelia and many carcinomas and that has been implicated in intercellular adhesion and metastasis. To gain insight into EpCAM function in a physiologic context in vivo, we generated conditional knockout mice with EpCAM-deficient LC and characterized them. Epidermis from these mice contained increased numbers of LC with normal levels of MHC and costimulatory molecules and T-cell-stimulatory activity in vitro. Migration of EpCAM-deficient LC from skin explants was inhibited, but chemotaxis of dissociated LC was not. Correspondingly, the ability of contact allergen-stimulated, EpCAM-deficient LC to exit epidermis in vivo was delayed, and strikingly fewer hapten-bearing LC subsequently accumulated in lymph nodes. Attenuated migration of EpCAM-deficient LC resulted in enhanced contact hypersensitivity responses as previously described in LC-deficient mice. Intravital microscopy revealed reduced translocation and dendrite motility in EpCAM-deficient LC in vivo in contact allergen-treated mice. These results conclusively link EpCAM expression to LC motility/migration and LC migration to immune regulation. EpCAM appears to promote LC migration from epidermis by decreasing LC-keratinocyte adhesion and may modulate intercellular adhesion and cell movement within in epithelia during development and carcinogenesis in an analogous fashion.
authors.affiliation: Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Gaiser
authors.forename: Tim
authors.initials: T
authors.lastname: Lämmermann
authors.forename: Xu
authors.initials: X
authors.lastname: Feng
authors.forename: Botond Z
authors.initials: BZ
authors.lastname: Igyarto
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Kaplan
authors.forename: Lino
authors.initials: L
authors.lastname: Tessarollo
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Germain
authors.forename: Mark C
authors.initials: MC
authors.lastname: Udey
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D003877:Dermatitis, Contact / Q000276:immunology / Q000473:pathology; D004817:Epidermis / Q000187:drug effects / Q000473:pathology*; D000071858:Epithelial Cell Adhesion Molecule; D005455:Fluorescent Antibody Technique; D007801:Langerhans Cells / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D003094:Collagen