Novel Mouse Models Based on Intersectional Genetics to Identify and Characterize Plasmacytoid Dendritic Cells

Overview

Journal Nat Immunol

Date 2023 Mar 17

PMID 36928414

Authors

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

Affiliations

Soon will be listed here.

Abstract

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 Zbtb46 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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