Differentiation of Langerhans Cells from Monocytes and Their Specific Function in Inducing IL-22-Specific Th Cells
Differentiation of Langerhans Cells from Monocytes and Their Specific Function in Inducing IL-22-Specific Th Cells
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DOI：
10.4049/jimmunol.1701402
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发表时间：
2018-11-15
影响因子：
4.4
通讯作者：
Takahashi, Hidemi
中科院分区：
文献类型：
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作者：
Otsuka, Yohei;Watanabe, Eri;Takahashi, Hidemi
人粘膜组织和皮肤含有两种不同类型的树突状细胞（DC）亚群，表皮朗格汉斯细胞（LC）和真皮DC，其可以分别通过C型凝集素受体Langerin和DC-SIGN的表达来区分。尽管外周血单核细胞分化成这些不同的亚群，但通过与GM-CSF、IL-4和TGF-β 1共培养诱导的单核细胞衍生的LC（moLC）共表达Langerin和DC-SIGN，表明环境线索仍不清楚。在这项研究中，我们发现LC分化是TGF-β 1依赖性的，辅助因子如IL-4和TNF-α促进TGF-β 1依赖性LC分化为Langerin（+）DC-SIGN（-）moLC，但持续暴露于IL-4会阻断分化。类固醇如地塞米松极大地增强了TNF-α诱导的moLC分化并阻断DC-SIGN表达。与原代LC一致，地塞米松处理的moLC表达CD 1a，而单核细胞衍生的DC（moDC）表达CD 1b、CD 1c和CD 1d。在分别用CD 1b和CD 1d配体分枝菌酸和α-半乳糖神经酰胺刺激后，moDCs而不是moLCs产生炎性细胞因子。引人注目的是，用角鲨烯触发moLC上的CD 1a而不是moDC上的CD 1a诱导了强烈的产生IL-22的CD 4（+）辅助T细胞应答。由于IL-22是维持皮肤稳态的重要细胞因子，因此这些数据表明LC上的CD 1a参与维持皮肤中的免疫屏障。
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 co-culture with GM-CSF, IL-4, and TGF-beta 1 coexpress both Langerin and DC-SIGN, suggesting that the environmental cues remain unclear. In this study, we show that LC differentiation is TGF-beta 1 dependent and that cofactors such as IL-4 and TNF-alpha promote TGF-beta 1-dependent LC differentiation into Langerin(+)DC-SIGN(-) moLCs but continuous exposure to IL-4 blocks differentiation. Steroids such as dexamethasone greatly enhanced TNF-alpha-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 alpha-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.