The CD83 reporter mouse elucidates the activity of the CD83 promoter in B, T, and dendritic cell populations in vivo
The CD83 reporter mouse elucidates the activity of the CD83 promoter in B, T, and dendritic cell populations in vivo
复制标题
DOI：
10.1073/pnas.0806335105
复制
发表时间：
2008-08-19
影响因子：
11.1
通讯作者：
Mak, Tak W.
中科院分区：
文献类型：
--
作者：
Lechmann, Matthias;Shuman, Naomi;Mak, Tak W.
CD83是鉴定成熟树突状细胞（DC）的主要表面标志物。在这项研究中，我们报告了在CD83启动子控制下表达EGFP的报告小鼠的产生。我们已经使用这些小鼠来表征体内和离体以及在稳态条件下和响应于Toll样受体（TLR）配体刺激的各种免疫系统细胞类型的CD83表达。用这些小鼠，我们可以在体内证明CD 83启动子在淋巴器官中的所有DC和B细胞中是高度活性的。有趣的是，这种启动子在B细胞中的活性主要取决于发育阶段，在晚期前B细胞阶段上调，并在所有外周B细胞中维持在高水平。我们还证实，这些细胞中的CD83主要是细胞内的，但在TLR刺激后上调。另外，T细胞中的CD 83启动子活性似乎依赖于刺激，并且可以主要在CD 4（+）CD 25（+）和CD 8（+）CD 25（+）T细胞以及CD 4（+）和CD 8（+）记忆细胞中发现。此外，我们还鉴定了人CD83剪接变体的鼠同源物。与人类相比，这些极其罕见的短转录本从未被发现没有高度显性的全长形式的表达。因此，小鼠CD83表面表达在体内主要是在免疫后调节的。我们的CD83报告小鼠代表了一种有用的小鼠模型，用于监测各种条件下DC和淋巴细胞的活化状态和迁移，我们的结果提供了急需的澄清CD83启动子活性的真实性质。
CD83 is the major surface marker identifying mature dendritic cells (DCs). In this study, we report the generation of reporter mice expressing EGFP under the control of the CD83 promoter. We have used these mice to characterize CD83 expression by various immune system cell types both in vivo and ex vivo and under steady-state conditions and in response to stimulation with a Toll-like receptor (TLR) ligand. With those mice we could prove in vivo that the CD83 promoter is highly active in all DCs and B cells in lymphoid organs. Interestingly, this promoter activity in B cells mainly depended on the stage of development, is up-regulated in the late pre-B cell stage, and was maintained on a high level in all peripheral B cells. We also confirmed that CD83 in those cells is mainly intracellular but is up-regulated after TLR stimulation. Otherwise, CD83 promoter activity in T cells seemed to depend on stimulation and could be found mainly in CD4(+)CD25(+) and CD8(+)CD25(+) T cells and in CD4(+) and CD8(+) memory cells. In addition, we identified the murine homologues of the human CD83 splice variants. In contrast to those in human, those extremely rare short transcripts were never found without the expression of the highly dominant full-length form. So, the murine CD83 surface expression is mainly regulated posttranslationally in vivo. Our CD83 reporter mice represent a useful mouse model for monitoring the activation status and migration of DCs and lymphocytes under various conditions, and our results provide much needed clarification of the true nature of CD83 promoter activity.