title: Functional involvement of E-cadherin in TGF-beta 1-induced cell cluster formation of in vitro developing human Langerhans-type dendritic cells.
abstract: Epithelial Langerhans cells (LC) represent immature dendritic cells that require TGF-beta 1 stimulation for their development. Little is known about the mechanisms regulating LC generation from their precursor cells. We demonstrate here that LC development from human CD34+ hemopoietic progenitor cells in response to TGF-beta 1 costimulation (basic cytokine combination GM-CSF plus TNF-alpha, stem cell factor, and Flt3 ligand) is associated with pronounced cell cluster formation of developing LC precursor cells. This cell-clustering phenomenon requires hemopoietic progenitor cell differentiation, since it is first seen on day 4 after culture initiation of CD34+ cells. Cell cluster formation morphologically indicates progenitor cell development along the LC pathway, because parallel cultures set up in the absence of exogenous TGF-beta 1 fail to form cell clusters and predominantly give rise to monocyte, but not LC, development (CD1a-, lysozyme+, CD14+). TGF-beta 1 costimulation of CD34+ cells induces neoexpression of the homophilic adhesion molecule E-cadherin in the absence of the E-cadherin heteroligand CD103. Addition of anti-E-cadherin mAb or mAbs to any of the constitutively expressed adhesion molecule (CD99, CD31, LFA-1, or CD18) to TGF-beta 1-supplemented progenitor cell cultures inhibits LC precursor cell cluster formation, and this effect is, with the exception of anti-E-cadherin mAb, associated with inhibition of LC generation. Addition of anti-E-cadherin mAb to the culture allows cell cluster-independent generation of LC from CD34+ cells. Thus, functional E-cadherin expression and homotypic cell cluster formation represent a regular response of LC precursor cells to TGF-beta 1 stimulation, and cytoadhesive interactions may modulate LC differentiation from hemopoietic progenitor cells.
authors.affiliation: Institute of Immunology, Vienna International Research Cooperation Center, Novartis Research Institute, Vienna, Austria.
authors.forename: E
authors.initials: E
authors.lastname: Riedl
authors.forename: J
authors.initials: J
authors.lastname: Stöckl
authors.forename: O
authors.initials: O
authors.lastname: Majdic
authors.forename: C
authors.initials: C
authors.lastname: Scheinecker
authors.forename: K
authors.initials: K
authors.lastname: Rappersberger
authors.forename: W
authors.initials: W
authors.lastname: Knapp
authors.forename: H
authors.initials: H
authors.lastname: Strobl
mesh_terms: D000071443:12E7 Antigen; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology; D018952:Antigens, CD34 / Q000096:biosynthesis; D018821:CD18 Antigens / Q000276:immunology; D015820:Cadherins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D006131:Growth Inhibitors / Q000276:immunology / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007801:Langerhans Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D000071443:12E7 Antigen; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018952:Antigens, CD34; D018821:CD18 Antigens; C061828:CD99 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D006131:Growth Inhibitors; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016212:Transforming Growth Factor beta