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一种新型细菌人工染色体转染的 podoplanin-cre 小鼠在体内靶向淋巴器官基质细胞。

A novel bacterial artificial chromosome-transgenic podoplanin-cre mouse targets lymphoid organ stromal cells in vivo.

机构信息

Institute of Immunobiology, Cantonal Hospital St. Gallen St. Gallen, Switzerland.

出版信息

Front Immunol. 2011 Oct 12;2:50. doi: 10.3389/fimmu.2011.00050. eCollection 2011.

DOI:10.3389/fimmu.2011.00050
PMID:22566840
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3342134/
Abstract

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.

摘要

基质细胞为次级淋巴器官 (SLO) 提供了结构基础,并调节白细胞在脾脏和淋巴结 (LNs) 的不同隔室中的进入和细胞迁移。此外,一些基质细胞亚群通过直接呈递抗原参与塑造 T 细胞反应。尽管人们对不同 SLO 驻留基质细胞亚群的生物学有了显著的了解,但它们的分子和功能特征仍然不完整。为了解决这一需求,我们生成了一种细菌人工染色体转基因小鼠模型,该模型利用足突蛋白 (pdpn) 启动子在 SLO 中的基质细胞中特异性表达 Cre 重组酶。Pdpn-Cre 小鼠的特征表明,转基因在 LNs 中的成纤维网状细胞和淋巴管内皮细胞亚群中表达。此外,该转基因促进了鉴定围绕中央动脉形成网状结构的新型脾脏血管周基质细胞亚群。对 Pdpn-Cre 小鼠中遗传标记的基质细胞中体内抗原表达的评估表明,MHC I 和 II 受限的 TCR 转基因 T 细胞均被激活。总之,基质细胞中的 pdpn-Cre 表达非常适合表征表型并剖析淋巴器官基质细胞的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f83/3342134/99290a14e99b/fimmu-02-00050-a001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f83/3342134/404eccc56d66/fimmu-02-00050-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f83/3342134/2e72d16d1a44/fimmu-02-00050-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f83/3342134/4eedceff4c91/fimmu-02-00050-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f83/3342134/160fe390bbb2/fimmu-02-00050-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f83/3342134/c908ba40cb4d/fimmu-02-00050-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f83/3342134/99290a14e99b/fimmu-02-00050-a001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f83/3342134/404eccc56d66/fimmu-02-00050-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f83/3342134/2e72d16d1a44/fimmu-02-00050-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f83/3342134/4eedceff4c91/fimmu-02-00050-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f83/3342134/160fe390bbb2/fimmu-02-00050-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f83/3342134/c908ba40cb4d/fimmu-02-00050-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f83/3342134/99290a14e99b/fimmu-02-00050-a001.jpg

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The stromal and haematopoietic antigen-presenting cells that reside in secondary lymphoid organs.存在于次级淋巴器官中的基质和造血抗原呈递细胞。
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Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation.
树突状细胞中干扰素-γ 受体信号转导抑制慢性淋巴缺失小鼠 CD4 T 细胞的自发性增殖。
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Podoplanin regulates the migration of mesenchymal stromal cells and their interaction with platelets.Podoplanin 调节间充质基质细胞的迁移及其与血小板的相互作用。
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