The final elimination step of self-reactive T cells occurs in the medulla of the thymus where a complex framework provided by stromal cells supports an optimal milieu for their selection. Here we present evidence that tight junctions (TJs) widely join medullary stromal cells of the human thymus. Occludin (OCLN) and claudin-1 (CLDN-1) of TJ-associated molecules were dominantly expressed in medullary thymic epithelial cells (mTECs), and CLDN-4 and CLDN-7 were also localized in some mTECs near Hassall's corpuscles. Interestingly, p53-like transcription factors were found to upregulate OCLN and CLDN-1 in human TEC lines, as recently suggested in the regulation of mTEC function. Furthermore, dendritic cells (DCs) of the medulla, with a major role for selection of thymocytes, expressed CLDN-1 and OCLN as well, implying that the interposition of DCs within the mTEC scaffold is also helped by TJs. Analysis of freeze-fracture replicas of the thymus revealed TJ strand structures in the vicinity of gap junction plaques through which small molecules might move, as implied by dye-transfer analysis of a medullary cell line. Thus, it is thought that p53-like molecules regulate TJ-associated interactions of medullary stromal cells and that this mechanism might be associated with an intercellular communication network, probably for preserving the medullary niches.

译文

:自我反应性T细胞的最终消除步骤发生在胸腺的髓质中,其中基质细胞提供的复杂框架为它们的选择提供了最佳环境。在这里,我们提供证据表明紧密连接(TJs)广泛加入人类胸腺的髓质基质细胞。 TJ相关分子的Occludin(OCLN)和claudin-1(CLDN-1)主要在髓样胸腺上皮细胞(mTECs)中表达,CLDN-4和CLDN-7也位于Hassall小体附近的某些mTECs中。有趣的是,正如最近在调控mTEC功能中所建议的那样,发现p53样转录因子可上调人TEC细胞系中的OCLN和CLDN-1。此外,在选择胸腺细胞中起主要作用的髓质树突状细胞(DC)也表达CLDN-1和OCLN,这暗示TJ也有助于mTEC支架内DC的插入。胸腺的冷冻断裂复制品的分析显示,在间隙连接斑块附近的TJ链结构中,小分子可能会通过间隙连接斑块移动,正如髓细胞系的染料转移分析所暗示的那样。因此,认为p53样分子调节髓质基质细胞的TJ相关相互作用,并且该机制可能与细胞间通讯网络有关,可能是为了保留髓ni。

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