法国图灵生命系统中心Michael Valente研究团队建立基于交叉遗传学的新型小鼠模型，以识别和表征浆细胞样树突状细胞(pDCs)。该研究于2023年3月16日发表于国际一流学术期刊《自然—免疫学》杂志上。

他们介绍了一种基于pDCs中独特的Siglech和Pacsin1共表达的交叉遗传学设计的报告小鼠pDC-Tom。pDC-Tom小鼠特异性地标记了pDCs，并与Zbtb46GFP小鼠杂交，使所有脾DC类型的转录组分析成为可能，揭示了在病毒感染期间pDC样细胞与移行DC (tDC)的分化激活。在感染期间，pDC-Tom小鼠的脾脏IFN+与IFN−pDCs的微解剖定位最初相似，但后来有所不同。他们报道的小鼠模型和特定的基因模块将有助于描述pDCs相对于其他DC类型的生理功能。

据悉，在病毒感染期间，pDCs是I型干扰素(IFN-I)的主要来源。它们的其他功能存在争议，因为缺乏在不影响DC样细胞和tDC的情况下在体内识别和靶向它们的工具，tDC具有重叠的表型和转录组，但对T细胞活化有更高的功效。

附：英文原文

Title: Novel mouse models based on intersectional genetics to identify and characterize plasmacytoid dendritic cells

Author: Valente, Michael, Collinet, Nils, Vu Manh, Thien-Phong, Popoff, Dimitri, Rahmani, Khalissa, Naciri, Karima, Bessou, Gilles, Rua, Rejane, Gil, Laurine, Mionnet, Cyrille, Milpied, Pierre, Tomasello, Elena, Dalod, Marc

Issue&Volume: 2023-03-16

Abstract: Plasmacytoid dendritic cells (pDCs) are the main source of type I interferon (IFN-I) during viral infections. Their other functions are debated, due to a lack of tools to identify and target them in vivo without affecting pDC-like cells and transitional DCs (tDCs), which harbor overlapping phenotypes and transcriptomes but a higher efficacy for T cell activation. In the present report, we present a reporter mouse, pDC-Tom, designed through intersectional genetics based on unique Siglech and Pacsin1 coexpression in pDCs. The pDC-Tom mice specifically tagged pDCs and, on breeding with Zbtb46GFP mice, enabled transcriptomic profiling of all splenic DC types, unraveling diverging activation of pDC-like cells versus tDCs during a viral infection. The pDC-Tom mice also revealed initially similar but later divergent microanatomical relocation of splenic IFN+ versus IFN pDCs during infection. The mouse models and specific gene modules we report here will be useful to delineate the physiological functions of pDCs versus other DC types.

DOI: 10.1038/s41590-023-01454-9

Source: https://www.nature.com/articles/s41590-023-01454-9