Showing papers by "Frederic Geissmann published in 2002"

Accumulation of immature Langerhans cells in human lymph nodes draining chronically inflamed skin.

Abstract: The coordinated migration and maturation of dendritic cells (DCs) such as intraepithelial Langerhans cells (LCs) is considered critical for T cell priming in response to inflammation in the periphery. However, little is known about the role of inflammatory mediators for LC maturation and recruitment to lymph nodes in vivo. Here we show in human dermatopathic lymphadenitis (DL), which features an expanded population of LCs in one draining lymph node associated with inflammatory lesions in its tributary skin area, that the Langerin/CD207+ LCs constitute a predominant population of immature DCs, which express CD1a, and CD68, but not CD83, CD86, and DC–lysosomal-associated membrane protein (LAMP)/CD208. Using LC-type cells generated in vitro in the presence of transforming growth factor (TGF)-β1, we further found that tumor necrosis factor (TNF)-α, as a prototype proinflammatory factor, and a variety of inflammatory stimuli and bacterial products, increase Langerin expression and Langerin dependent Birbeck granules formation in cell which nevertheless lack costimulatory molecules, DC–LAMP/CD208 and potent T cell stimulatory activity but express CCR7 and respond to the lymph node homing chemokines CCL19 and CCL21. This indicates that LC migration and maturation can be independently regulated events. We suggest that during DL, inflammatory stimuli in the skin increase the migration of LCs to the lymph node but without associated maturation. Immature LCs might regulate immune responses during chronic inflammation.

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

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.