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A Novel Bacterial Artificial Chromosome-Transgenic Podoplanin–Cre Mouse Targets Lymphoid Organ Stromal Cells in vivo

机译:一种新型细菌人工染色体转基因Podoplanin-Cre小鼠体内靶向淋巴器官基质细胞。

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摘要

Stromal cells provide the structural foundation of secondary lymphoid organs (SLOs), and regulate leukocyte access and cell migration within the different compartments of spleen and lymph nodes (LNs). Furthermore, several stromal cell subsets have been implied in shaping of T cell responses through direct presentation of antigen. Despite significant gain of knowledge on the biology of different SLO-resident stromal cell subsets, their molecular and functional characterization has remained incomplete. To address this need, we have generated a bacterial artificial chromosome-transgenic mouse model that utilizes the podoplanin (pdpn) promoter to express the Cre-recombinase exclusively in stromal cells of SLOs. The characterization of the Pdpn–Cre mouse revealed transgene expression in subsets of fibroblastic reticular cells and lymphatic endothelial cells in LNs. Furthermore, the transgene facilitated the identification of a novel splenic perivascular stromal cell subpopulation that forms web-like structures around central arterioles. Assessment of the in vivo antigen expression in the genetically tagged stromal cells in Pdpn–Cre mice revealed activation of both MHC I and II-restricted TCR transgenic T cells. Taken together, stromal pdpn–Cre expression is well-suited to characterize the phenotype and to dissect the function of lymphoid organ stromal cells.
机译:基质细胞提供次级淋巴器官(SLO)的结构基础,并调节脾脏和淋巴结(LN)不同隔室内的白细胞进入和细胞迁移。此外,通过直接呈递抗原,在T细胞反应的形成中暗示了几个基质细胞亚群。尽管获得了大量关于不同SLO驻留基质细胞亚群的生物学知识,但它们的分子和功能表征仍然不完整。为了满足这一需求,我们已经建立了一个细菌人工染色体转基因小鼠模型,该模型利用podoplanin(pdpn)启动子在SLO的基质细胞中专门表达Cre重组酶。 Pdpn–Cre小鼠的特征揭示了LNs中成纤维细胞网状细胞和淋巴管内皮细胞亚群的转基因表达。此外,转基因促进了新的脾脏血管周围基质细胞亚群的鉴定,该亚群在中央小动脉周围形成了网状结构。评估Pdpn-Cre小鼠中遗传标记的基质细胞中的体内抗原表达后,发现MHC I和II限制性TCR转基因T细胞均被激活。两者合计,基质pdpn–Cre表达非常适合表征表型和解剖淋巴器官基质细胞的功能。

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