Antagonistic effects of IL-4 and TGF-beta1 on Langerhans cell-related antigen expression by human monocytes.
In this study, we analyzed the specific effects of transforming growth factor beta (TGF-beta1) and/or IL-4 on monocyte-derived cells. Monocytes were cultured with GM-CSF, GM-CSF/TGF-beta1, GM-CSF/IL-4, or GM-CSF/IL-4/TGF-beta1 before cell morphology, phenotype, and function were assessed. As expected, interleukin-4 is mandatory for monocyte differentiation into potent allostimulatory DC. In its absence, monocyte-derived cells share many phenotypic and functional features with macrophages. However, it is interesting that the cells express E-cadherin, independent of exogenous TGF-beta1, and addition of the cytokine induced CCR6 expression. Most importantly, a subset of monocytes cultured with GM-CSF/TGF-beta1 expresses Langerin, as confirmed by electron microscopy analysis. Langerin engagement with specific monoclonal antibodies induces its internalization and the formation of typical Birbeck granules. Monocytes cultured in GM-CSF/IL-4 did not express the LC markers E-cadherin, CCR6, or Langerin. The simultaneous addition of TGF-beta1 allows most of the cells to express E-cadherin but rarely CCR6 and Langerin. Taken together, the results add further evidence that LC can derive from monocytes and demonstrate an antagonistic effect of IL-4 and TGF-beta1 on monocyte differentiation toward the LC pathway.
Guironnet
G
G
Department of Dermatology, INSERM U346, Hôpital E. Herriot, Lyon, France.
Dezutter-Dambuyant
C
C
Vincent
C
C
Bechetoille
N
N
Schmitt
D
D
Péguet-Navarro
J
J
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D000954:Antigens, Surface / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D003713:Dendritic Cells / Q000276:immunology; D004705:Endocytosis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000494:pharmacology*; D037181:Lectins, C-Type; D007959:Lymphocyte Culture Test, Mixed; D037241:Mannose-Binding Lectins; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000954:Antigens, Surface; C121916:CD207 protein, human; D019013:CD40 Antigens; D015820:Cadherins; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor