Requirement of interaction between mast cells and skin dendritic cells to establish contact hypersensitivity.
Requirement of interaction between mast cells and skin dendritic cells to establish contact hypersensitivity.
复制标题
肥大细胞与皮肤树突状细胞之间相互作用的要求以建立接触性超敏反应。
DOI：
10.1371/journal.pone.0025538
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Kabashima K
中科院分区：
文献类型：
--
作者：
Otsuka A;Kubo M;Honda T;Egawa G;Nakajima S;Tanizaki H;Kim B;Matsuoka S;Watanabe T;Nakae S;Miyachi Y;Kabashima K
肥大细胞（MC）在接触性超敏反应（CHS）中的作用仍存在争议。这部分是由于使用MC缺陷Kit W/Wv小鼠模型，因为Kit W/Wv小鼠由于c-kit中的点突变而先天缺乏其他类型的细胞。最近的一项研究表明，IL 4基因转录的内含子增强子（IE）对MC是必需的，但在其他细胞类型中不是必需的。本研究的目的是重新评估MC在CHS中的作用，使用小鼠，其中MC可以有条件地和特异性地耗尽。其中MC被有条件地耗尽的转基因Mas-TRECK小鼠是使用通过IE的细胞类型特异性基因调控新产生的。使用该小鼠，分析CHS和FITC诱导的皮肤DC迁移。采用骨髓来源的树突状细胞（BMDCs）与骨髓来源的MCs共培养的方法，进行趋化性测定和胞浆Ca 2+显像。在Mas-TRECK小鼠中，当在致敏阶段MCs耗尽时，CHS减弱。此外，皮肤DC的成熟和迁移都被MC耗尽所废除。BMMCs以ICAM-1和TNF-α依赖的方式促进BMDC的成熟和趋化，刺激BMDCs后，与MC直接相互作用时，MC内Ca ~（2+）增加，BMMCs膜结合TNF-α上调。这些结果表明，MCs通过与皮肤中的DC相互作用以建立CHS的致敏相来增强DC功能。
The role of mast cells (MCs) in contact hypersensitivity (CHS) remains controversial. This is due in part to the use of the MC-deficient Kit W/Wv mouse model, since Kit W/Wv mice congenitally lack other types of cells as a result of a point mutation in c-kit. A recent study indicated that the intronic enhancer (IE) for Il4 gene transcription is essential for MCs but not in other cell types. The aim of this study is to re-evaluate the roles of MCs in CHS using mice in which MCs can be conditionally and specifically depleted. Transgenic Mas-TRECK mice in which MCs are depleted conditionally were newly generated using cell-type specific gene regulation by IE. Using this mouse, CHS and FITC-induced cutaneous DC migration were analyzed. Chemotaxis assay and cytoplasmic Ca2+ imaging were performed by co-culture of bone marrow-derived MCs (BMMCs) and bone marrow-derived dendritic cells (BMDCs). In Mas-TRECK mice, CHS was attenuated when MCs were depleted during the sensitization phase. In addition, both maturation and migration of skin DCs were abrogated by MC depletion. Consistently, BMMCs enhanced maturation and chemotaxis of BMDC in ICAM-1 and TNF-α dependent manners Furthermore, stimulated BMDCs increased intracellular Ca2+ of MC upon direct interaction and up-regulated membrane-bound TNF-α on BMMCs. These results suggest that MCs enhance DC functions by interacting with DCs in the skin to establish the sensitization phase of CHS.