IL-13 Is More Efficient than IL-4 for Recruiting Langerhans Cell Precursors from Peripheral CD14+ Monocytes

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Abstract
Background: GM-CSF, IL-4 and TGF-β1 can drive the differentiation of CD14+ monocytes towards the immature Langerhans (LC) dendritic cell (DC) pathway. Their in vivo epidermal LC counterparts are mainly identified by the langerin molecules which are cross-linked into Birbeck granules (BG) upon mannose residue activation. Objective: The IL-13 and IL-14 cytokines sharing similar anti-inflammatory/immune functions, we investigated whether IL-13 (plus GM-CSF/TGF-β1) can substitute for IL-4 to preferentially skew the CD14+ monocyte differentiation towards LC. Methods: CD14+ monocytes cultured in the presence of GM-CSF/TGF-β1/IL-13 (IL-13-DC) for 6 days were then compared to GM-CSF/TGF-β1/IL-4-generated LC (IL-4-DC) by studying their phenotype, ultrastructural and functional features. Results: IL-13, in synergy with GM-CSF/TGF-β1, induced CD14+ monocytes to differentiate into LC after a short TNF-α stimulation more efficiently than IL-4. IL-13-DC are more immature than IL- 4-DC, as shown by both their preserved expression of monocyte markers (CD14, CD68) and their strong capacity of FITC-dextran uptake. Conclusion: IL-13 in combination with GM-CSF/TGF-β1/TNF-α favors CD14+ monocyte differentiation into LC which display numerous BG.