The Cooperative Role of CD326+ and CD11b+ Dendritic Cell Subsets for a Hapten-Induced Th2 Differentiation
The Cooperative Role of CD326+ and CD11b+ Dendritic Cell Subsets for a Hapten-Induced Th2 Differentiation
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DOI：
10.4049/jimmunol.1601262
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发表时间：
2017-11-01
影响因子：
4.4
通讯作者：
Kang, Suk-Jo
中科院分区：
文献类型：
--
作者：
Cho, Yuri;Kwon, Dohyeong;Kang, Suk-Jo
树突状细胞（Dendritic cells，DC）在介导免疫应答中发挥重要作用。以前的研究已经确定了各种DC亚群，并阐明了其上下文依赖的功能，平行效应Th细胞亚群。然而，很少有人知道的DC亚群负责分化的Th 2细胞的过敏性接触性皮炎。在这项研究中，我们试图确定介导半抗原致敏小鼠中Th 2启动的DC亚群。我们诱导半抗原特异性的Th 2分化的小鼠与一个单一的应用程序的FITC溶解在丙酮：邻苯二甲酸二乙酯致敏，并跟踪免疫细胞负责诱导Th 2分化过程中的主要刺激，使我们能够跟踪Th 2启动在体内，并删除嗜碱性粒细胞和特定的DC亚群。我们的分析表明，IL-4在体内产生早在第3天从CD 4（+）T细胞与一个单一的应用程序的FITC。嗜碱性粒细胞，尽管产生IL-4比T细胞早1天，被发现是Th 2分化的障碍。相反，我们证明了CD 326（+）真皮DC和朗格汉斯细胞是FIT-C诱导的Th 2分化所必需的。此外，CD 326（+）Langerhans细胞和CD 11b（+）DCs在体外协同诱导幼稚T细胞分化为Th 2细胞。总的来说，我们的研究结果强调了至少两个DC亚群，它们在将幼稚CD 4（+）T细胞极化为Th 2细胞中起关键作用，并支持Th 2分化的两次打击模型。
Dendritic cells (DCs) play a critical role in directing immune responses. Previous studies have identified a variety of DC subsets and elucidated their context-dependent functions that parallel those of effector Th cell subsets. However, little is known about the DC subsets responsible for differentiation of Th2 cells governing allergic contact dermatitis. In this study, we sought to determine the DC subset(s) that mediate Th2 priming in hapten-sensitized mice. We induced hapten-specific Th2 differentiation by sensitizing the mice with a single application of FITC dissolved in acetone: dibutyl phthalate, and traced the immune cells responsible for inducing the Th2 differentiation process at the primary stimulation, enabling us to track Th2 priming in vivo and to delete basophils and specific DC subsets. Our analysis revealed that IL-4 was produced in vivo as early as day 3 from CD4(+) T cells with a single application of FITC. Basophils, despite producing IL-4 1 d earlier than T cells, were found to be dispensable for Th2 differentiation. Instead, we demonstrated that CD326(+) dermal DCs and Langerhans cells were redundantly required for FIT-Cinduced Th2 differentiation in vivo. Moreover, the cooperation of CD326(+) Langerhans cells and CD11b(+) DCs differentiated naive T cells into Th2 cells in vitro. Collectively, our findings highlight at least two DC subsets that play a critical role in polarizing naive CD4(+) T cells to Th2 cells and support a two-hit model for Th2 differentiation.