A fluorescent reporter model for the visualization and characterization of TDC

TDC are hematopoietic cells that combine dendritic cell (DC) and conventional T cell markers and functional properties. They were identified in secondary lymphoid organs (SLOs) of naïve mice as cells expressing CD11c, major histocompatibility molecule (MHC)-II, and the T cell receptor (TCR)  chain. Despite thorough characterization as to their potential functional properties, a physiological role for TDC remains to be determined. Unfortunately, using CD11c as a marker for TDC has the caveat of its upregulation on different cells, including T cells, upon activation. Therefore, a more specific marker is needed to further investigate TDC functions in peripheral organs in different pathological settings. Here we took advantage of Zbtb46-GFP reporter mice to explore the frequency and localization of TDC in peripheral tissues at steady state and upon viral infection. RNA sequencing analysis confirmed that TDC identified with this reporter model have a gene signature that is distinct from conventional T cells and DC. In addition, frequency and total numbers of TDC in the SLOs recapitulated those found using CD11c as a marker. This reporter model allowed for identification of TDC in situ not only in SLOs but also in the liver and lung of naïve mice. Interestingly, we found that TDC numbers in the SLOs increased upon viral infection, suggesting that TDC might play a role during viral infections. In conclusion, we propose a visualization strategy that might shed light on the physiological role of TDC in several pathological contexts, including infection and cancer.

TDC（树突状细胞相关T细胞）是一类兼具树突状细胞（DC）和传统T细胞标志物及功能特性的造血细胞。它们在未接触过抗原的幼鼠的次级淋巴器官（SLOs）中被鉴定为表达CD11c、主要组织相容性分子（MHC）-II和T细胞受体（TCR）β链的细胞。尽管对其潜在的功能特性已进行了详尽的描述，但TDC的生理作用尚待确定。遗憾的是，以CD11c作为TDC标志物存在其局限性，即其在激活后会在包括T细胞在内的多种细胞上上调。因此，需要一种更特异的标志物来进一步研究TDC在不同病理状态下的外周器官功能。本研究利用Zbtb46-GFP报告小鼠的优势，探讨了TDC在稳态和病毒感染后外周组织的频率和定位。RNA测序分析证实，使用此报告模型鉴定的TDC具有与常规T细胞和DC不同的基因特征。此外，SLOs中TDC的频率和总数与使用CD11c作为标志物时观察到的一致。此报告模型不仅允许在SLOs中，而且能够在幼鼠的肝脏和肺中定位TDC。有趣的是，我们发现病毒感染后SLOs中的TDC数量增加，这表明TDC可能在病毒感染过程中发挥作用。综上所述，我们提出了一种可视化策略，该策略可能有助于阐明TDC在包括感染和癌症在内的多种病理环境中的生理作用。