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

Area of Science:

• Immunology
• Cell Biology
• Virology

Background:

• Plasmacytoid dendritic cells (pDCs) are primary producers of type I interferon (IFN-I) during viral infections.
• Existing tools lack specificity, hindering the in vivo study of pDCs without affecting similar cell types like transitional DCs (tDCs).
• Overlapping phenotypes and transcriptomes between pDCs and tDCs complicate functional differentiation.

Purpose of the Study:

• To develop a novel reporter mouse model for specific pDC identification and study.
• To enable transcriptomic profiling and functional analysis of pDCs and other splenic dendritic cell subsets.
• To investigate the distinct roles and behaviors of pDCs during viral infections.

Main Methods:

• Development of the pDC-Tom reporter mouse using intersectional genetics based on Siglech and Pacsin1 coexpression.
• Breeding pDC-Tom mice with Zbtb46^GFP mice for comprehensive splenic DC transcriptomic analysis.
• In vivo tracking and analysis of pDC migration and interferon production during viral infection.

Main Results:

• The pDC-Tom mice specifically and accurately tagged pDCs.
• Transcriptomic profiling revealed distinct activation patterns between pDC-like cells and tDCs during viral infection.
• Observation of divergent microanatomical relocation of IFN⁺ versus IFN^- pDCs within the spleen during infection.

Conclusions:

• The pDC-Tom reporter mouse model provides a crucial tool for specific pDC research.
• The study highlights diverging activation and migration patterns of pDCs and related DC subsets during viral challenges.
• These findings will advance the understanding of pDC-specific functions versus those of other dendritic cell types.