Department of Dermatology, INSERM U346, Hôpital E. Herriot, Lyon, France
Correspondence: J. Péguet-Navarro, Department of Dermatology, INSERM U346, Hôpital E. Herriot, Lyon, France. E-mail: peguet{at}lyon151.inserm.fr
In this study, we analyzed the specific effects of transforming growth factor ß (TGF-ß1) and/or IL-4 on monocyte-derived cells. Monocytes were cultured with GM-CSF, GM-CSF/TGF-ß1, GM-CSF/IL-4, or GM-CSF/IL-4/TGF-ß1 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-ß1, and addition of the cytokine induced CCR6 expression. Most importantly, a subset of monocytes cultured with GM-CSF/TGF-ß1 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-ß1 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-ß1 on monocyte differentiation toward the LC pathway.
Key Words: IL-4 • dendritic cells • E-cadherin • langerin
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