CD34+ cell-derived CD14+ precursor cells develop into Langerhans cells in a TGF-beta 1-dependent manner.
Langerhans cells (LC) are CD1a+E-cadherin (E-cad)+Birbeck granule+ but CD11b-CD36-factor XIIIa (FXIIIa)- members of the dendritic cell (DC) family. Evidence holds that LC originate from CD1a+CD14- rather than CD14+CD1a- progenitors, both of which arise from GM-CSF/TNF-alpha-stimulated CD34+ stem cells. The CD14+CD1a- progenitors, on the other hand, can give rise to a separate DC type characterized by its CD1a+CD11b+CD36+FXIIIa+E-cad-BG- phenotype (non-LC DC). Although GM-CSF/TNF-alpha are important for both LC and non-LC DC differentiation, TGF-beta 1 is thought to preferentially promote LC development in vitro and in vivo. However, the hemopoietic biology of this process and the nature of TGF-beta 1-responsive LC precursors (LCp) are not well understood. Here we show that CD14+ precursors in the presence, but not in the absence, of TGF-beta 1 give rise to a progeny that fulfills all major criteria of LC. In contrast, LC development from CD1a+ progenitors was TGF-beta 1 independent. Further studies revealed that CD14+ precursors contain a CD11b+ and a CD11b- subpopulation. When either subset was stimulated with GM-CSF/TNF-alpha and TGF-beta 1, only CD14+CD11b- cells differentiated into LC. The CD11b+ cells, on the other hand, acquired non-LC DC features only. The higher doubling rates of cells entering the CD14+ LCp rather than the CD1a+ LCp pathway add to the importance of TGF-beta 1 for LC development. Because CD14+CD11b- precursors are multipotent cells that can enter LC or macrophage differentiation, it is suggested that these cells, if present at the tissue level, endow a given organ with the property to generate diverse cell types in response to the local cytokine milieu.
Jaksits
S
S
Division of Immunology, Allergy, and Infectious Diseases, Department of Dermatology, University of Vienna Medical School, Austria.
Kriehuber
E
E
Charbonnier
A S
AS
Rappersberger
K
K
Stingl
G
G
Maurer
D
D
D000328:Adult; D018949:Antigens, CD1 / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis*; D000954:Antigens, Surface / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000276:immunology / Q000648:ultrastructure; D003713:Dendritic Cells / Q000276:immunology / Q000648:ultrastructure; D005312:Fetal Blood / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007399:Interphase / Q000276:immunology; D007801:Langerhans Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000502:physiology*
D018949:Antigens, CD1; D018952:Antigens, CD34; D000954:Antigens, Surface; D018950:Lipopolysaccharide Receptors; D016212:Transforming Growth Factor beta