title: Human blood BDCA-1 dendritic cells differentiate into Langerhans-like cells with thymic stromal lymphopoietin and TGF-β.
abstract: The ontogeny of human Langerhans cells (LCs) remains poorly characterized, in particular the nature of LC precursors and the factors that may drive LC differentiation. Here we report that thymic stromal lymphopoietin (TSLP), a keratinocyte-derived cytokine involved in epithelial inflammation, cooperates with transforming growth factor (TGF)-β for the generation of LCs. We show that primary human blood BDCA-1(+), but not BDCA-3(+), dendritic cells (DCs) stimulated with TSLP and TGF-β harbor a typical CD1a(+)Langerin(+) LC phenotype. Electron microscopy established the presence of Birbeck granules, an intracellular organelle specific to LCs. LC differentiation was not observed from tonsil BDCA-1(+) and BDCA-3(+) subsets. TSLP + TGF-β LCs had a mature phenotype with high surface levels of CD80, CD86, and CD40. They induced a potent CD4(+) T-helper (Th) cell expansion and differentiation into Th2 cells with increased production of tumor necrosis factor-α and interleukin-6 compared with CD34-derived LCs. Our findings establish a novel LC differentiation pathway from BDCA-1(+) blood DCs with potential implications in epithelial inflammation. Therapeutic targeting of TSLP may interfere with tissue LC repopulation from circulating precursors.
authors.affiliation: Department of Biopathology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France; Research Section, Institut Curie, Paris, France; and Centre d 'Investigations Cliniques Institut Gustave Roussy Curie 1428, Paris, France.
authors.forename: Carolina
authors.initials: C
authors.lastname: Martínez-Cingolani
authors.affiliation: Department of Biopathology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France; Research Section, Institut Curie, Paris, France; and Centre d 'Investigations Cliniques Institut Gustave Roussy Curie 1428, Paris, France.
authors.forename: Maximilien
authors.initials: M
authors.lastname: Grandclaudon
authors.affiliation: Department of Biopathology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France; Research Section, Institut Curie, Paris, France; and.
authors.forename: Marine
authors.initials: M
authors.lastname: Jeanmougin
authors.affiliation: Department of Biopathology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France; Research Section, Institut Curie, Paris, France; and.
authors.forename: Mabel
authors.initials: M
authors.lastname: Jouve
authors.affiliation: Department of Biopathology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France; Research Section, Institut Curie, Paris, France; and.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Zollinger
authors.affiliation: Department of Biopathology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France; Research Section, Institut Curie, Paris, France; and Centre d 'Investigations Cliniques Institut Gustave Roussy Curie 1428, Paris, France.
authors.forename: Vassili
authors.initials: V
authors.lastname: Soumelis
mesh_terms: D018949:Antigens, CD1 / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D016207:Cytokines / Q000494:pharmacology*; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007801:Langerhans Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D012867:Skin / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D018949:Antigens, CD1; C437944:CD1C protein, human; D016207:Cytokines; D006023:Glycoproteins; D016212:Transforming Growth Factor beta; D000094632:Thymic Stromal Lymphopoietin