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

Publié dans: Nat Immunol 2023 Apr; 24(4): 714-728

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

Résumé

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.

Lien vers HAL – hal-04235641

Lien vers le DOI – 10.1038/s41590-023-01454-9