Dermal-resident CD14+ cells differentiate into Langerhans cells.
Epidermal Langerhans cells (LCs) show extraordinary immunostimulatory capacity and play a key role in the initiation and regulation of immune responses. Studies of LC biology are currently the focus of efforts to engineer immune responses and to better understand the immunopathology of cutaneous diseases. Here we identified and characterized a population of LC precursors that were resident in human skin. These immediate precursors expressed CD14, langerin and functional CCR6. When cultured with transforming growth factor-beta1 alone, they had the potential to differentiate into epidermal LCs; when cultured in the presence of granulocyte macrophage-colony-stimulating factor and interleukin 4 they differentiated into functionally mature dendritic cells. Identification and characterization of these LC precursors provided insight into LC biology and the mechanism(s) through which LCs repopulate the epidermis.
Larregina
A T
AT
Department of Dermatology and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 USA. adrianal@pitt.edu
Morelli
A E
AE
Spencer
L A
LA
Logar
A J
AJ
Watkins
S C
SC
Thomson
A W
AW
Falo
L D
LD
D000941:Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000494:pharmacology; D002633:Chemotaxis; D016207:Cytokines / Q000494:pharmacology; D020405:Dermis / Q000166:cytology*; D004705:Endocytosis; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007801:Langerhans Cells / Q000145:classification / Q000276:immunology* / Q000648:ultrastructure*; D018950:Lipopolysaccharide Receptors / Q000032:analysis* / Q000276:immunology; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000096:biosynthesis; D012867:Skin / Q000276:immunology*; D013234:Stem Cells / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure
D000941:Antigens; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine