Αρχειοθήκη ιστολογίου

Δευτέρα 5 Νοεμβρίου 2018

Differentiation of Langerhans Cells from Monocytes and Their Specific Function in Inducing IL-22-Specific Th Cells [INNATE IMMUNITY AND INFLAMMATION]

Human mucosal tissues and skin contain two distinct types of dendritic cell (DC) subsets, epidermal Langerhans cells (LCs) and dermal DCs, which can be distinguished by the expression of C-type lectin receptors, Langerin and DC-SIGN, respectively. Although peripheral blood monocytes differentiate into these distinct subsets, monocyte-derived LCs (moLCs) induced by coculture with GM-CSF, IL-4, and TGF-β1 coexpress both Langerin and DC-SIGN, suggesting that the environmental cues remain unclear. In this study, we show that LC differentiation is TGF-β1 dependent and that cofactors such as IL-4 and TNF-α promote TGF-β1–dependent LC differentiation into Langerin+DC-SIGN moLCs but continuous exposure to IL-4 blocks differentiation. Steroids such as dexamethasone greatly enhanced TNF-α–induced moLC differentiation and blocked DC-SIGN expression. Consistent with primary LCs, dexamethasone-treated moLCs express CD1a, whereas monocyte-derived DCs (moDCs) express CD1b, CD1c, and CD1d. moDCs but not moLCs produced inflammatory cytokines after stimulation with CD1b and CD1d ligands mycolic acid and α-galactosylceramide, respectively. Strikingly, CD1a triggering with squalene on moLCs but not moDCs induced strong IL-22-producing CD4+ helper T cell responses. As IL-22 is an important cytokine in the maintenance of skin homeostasis, these data suggest that CD1a on LCs is involved in maintaining the immune barrier in the skin.



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