title: CD1c+ blood dendritic cells have Langerhans cell potential.
abstract: Langerhans cells (LCs) are self-renewing in the steady state but repopulated by myeloid precursors after injury. Human monocytes give rise to langerin-positive cells in vitro, suggesting a potential precursor role. However, differentiation experiments with human lineage-negative cells and CD34(+) progenitors suggest that there is an alternative monocyte-independent pathway of LC differentiation. Recent data in mice also show long-term repopulation of the LC compartment with alternative myeloid precursors. Here we show that, although monocytes are able to express langerin, when cultured with soluble ligands granulocyte macrophage colony-stimulating factor (GM-CSF), transforming growth factor β (TGFβ), and bone morphogenetic protein 7 (BMP7), CD1c(+) dendritic cells (DCs) become much more LC-like with high langerin, Birbeck granules, EpCAM, and E-cadherin expression under the same conditions. These data highlight a new potential precursor function of CD1c(+) DCs and demonstrate an alternative pathway of LC differentiation that may have relevance in vivo.
authors.affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Milne
authors.affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Venetia
authors.initials: V
authors.lastname: Bigley
authors.affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Merry
authors.initials: M
authors.lastname: Gunawan
authors.affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Muzlifah
authors.initials: M
authors.lastname: Haniffa
authors.affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Collin
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D018949:Antigens, CD1 / Q000378:metabolism*; D001773:Blood Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007801:Langerhans Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018949:Antigens, CD1; D055419:Bone Morphogenetic Protein 7; C437944:CD1C protein, human; C121916:CD207 protein, human; D015820:Cadherins; D006023:Glycoproteins; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D016212:Transforming Growth Factor beta; D016178:Granulocyte-Macrophage Colony-Stimulating Factor