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

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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

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

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