Differentiation of Langerhans Cells from Monocytes and Their Specific Function in Inducing IL-22-Specific Th Cells.

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.

Otsuka Y ，Watanabe E ，Shinya E ，Okura S ，Saeki H ，Geijtenbeek TBH ，Takahashi H ... -  《-》

Human epidermal Langerhans cells differ from monocyte-derived Langerhans cells in CD80 expression and in secretion of IL-12 after CD40 cross-linking.

Peiser M ，Wanner R ，Kolde G 《JOURNAL OF LEUKOCYTE BIOLOGY》

Differences in T-helper polarizing capability between human monocyte-derived dendritic cells and monocyte-derived Langerhans'-like cells.

Rajkovic I ，Dragicevic A ，Vasilijic S ，Bozic B ，Dzopalic T ，Tomic S ，Majstorovic I ，Vucevic D ，Djokic J ，Balint B ，Colic M ... -  《-》

Notch-Mediated Generation of Monocyte-Derived Langerhans Cells: Phenotype and Function.

Langerhans cells (LCs) in the skin are a first line of defense against pathogens but also play an essential role in skin homeostasis. Their exclusive expression of the C-type lectin receptor Langerin makes them prominent candidates for immunotherapy. For vaccine testing, an easily accessible cell platform would be desirable as an alternative to the time-consuming purification of LCs from human skin. Here, we present such a model and demonstrate that monocytes in the presence of GM-CSF, TGF-β1, and the Notch ligand DLL4 differentiate within 3 days into CD1a+Langerin+cells containing Birbeck granules. RNA sequencing of these monocyte-derived LCs (moLCs) confirmed gene expression of LC-related molecules, pattern recognition receptors, and enhanced expression of genes involved in the antigen-presenting machinery. On the protein level, moLCs showed low expression of costimulatory molecules but prominent expression of C-type lectin receptors. MoLCs can be matured, secrete IL-12p70 and TNF-α, and stimulate proliferation and cytokine production in allogeneic CD4+ and CD8+ T cells. In regard to vaccine testing, a recently characterized glycomimetic Langerin ligand conjugated to liposomes demonstrated specific and fast internalization into moLCs. Hence, these short-term in vitro‒generated moLCs represent an interesting tool to screen LC-based vaccines in the future.

Bellmann L ，Zelle-Rieser C ，Milne P ，Resteu A ，Tripp CH ，Hermann-Kleiter N ，Zaderer V ，Wilflingseder D ，Hörtnagl P ，Theochari M ，Schulze J ，Rentzsch M ，Del Frari B ，Collin M ，Rademacher C ，Romani N ，Stoitzner P ... -  《-》

Mixed Langerhans cell and interstitial/dermal dendritic cell subsets emanating from monocytes in Th2-mediated inflammatory conditions respond differently to proinflammatory stimuli.

Bechetoille N ，André V ，Valladeau J ，Perrier E ，Dezutter-Dambuyant C ... -  《JOURNAL OF LEUKOCYTE BIOLOGY》