A fluorescent reporter model for the visualization and characterization of TDC

Abstract

AbstractTDCare 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) β chain. Despite thorough characterization as to their potential functional properties, a physiological role for TDCremains to be determined. Unfortunately, using CD11c as a marker for TDChas the caveat of its upregulation on different cells, including T cells, upon activation. Therefore, a more specific marker is needed to further investigate TDCfunctions in peripheral organs in different pathological settings. Here we took advantage of Zbtb46-GFP reporter mice to explore the frequency and localization of TDCin peripheral tissues at steady state and upon viral infection. RNA sequencing analysis confirmed that TDCidentified with this reporter model have a gene signature that is distinct from conventional T cells and DC. In addition, frequency and total numbers of TDCin the SLOs recapitulated those found using CD11c as a marker. This reporter model allowed for identification of TDCin situ not only in SLOs but also in the liver and lung of naïve mice. Interestingly, we found that TDCnumbers in the SLOs increased upon viral infection, suggesting that TDCmight play a role during viral infections. In conclusion, we propose a visualization strategy that might shed light on the physiological role of TDCin several pathological contexts, including infection and cancer.