Dendritic cell type 3 arises from Ly6C+ monocyte-dendritic cell progenitors

• DOI: 10.1016/j.immuni.2023.07.001
• Publication Date: 2023-07-27T16:32:12Z
• Authors: Zhaoyuan Liu; Haiting Wang; Ziyi Li; Regine J. Dress; Yiwen Zhu; Shuangyan Zhang; Donatella De Feo; Wan Ting Kong; Peiliang Cai; Amanda Shin; Cécile Piot; Jiangyan Yu; Yaqi Gu; Mingnan Zhang; Caixia Gao; Lei Chen; Honglin Wang; Mathias Vétillard; Pierre Guermonprez; Immanuel Kwok; Lai Guan Ng; Svetoslav Chakarov; Andreas Schlitzer; Burkhard Becher; Charles-Antoine D...; Bing Su; Florent Ginhoux
• Keywords: 610 Medicine & health; 10263 Institute of Experimental Immunology; DC1; DC; DC2; Monocytes; DC3; Mice; MDP; Humans; Animals; dendritic cells; Cells, Cultured; pre; 2403 Immunology; DC progenitors; pro; Stem Cells; Cell Differentiation; 2725 Infectious Diseases; Dendritic Cells; Phenotype; monocyte; 2723 Immunology and Allergy; 570 Life sciences; biology; fate mapping; monocytes

Conventional dendritic cells (cDCs) are professional antigen-presenting cells that control the adaptive immune response. Their subsets and developmental origins have been intensively investigated but are still not fully understood as their phenotypes, especially in the DC2 lineage and the recently described human DC3s, overlap with monocytes. Here, using LEGENDScreen to profile DC vs. monocyte lineages, we found sustained expression of FLT3 and CD45RB through the whole DC lineage, allowing DCs and their precursors to be distinguished from monocytes. Using fate mapping models, single-cell RNA sequencing and adoptive transfer, we identified a lineage of murine CD16/32+CD172a+ DC3, distinct from DC2, arising from Ly6C+ monocyte-DC progenitors (MDPs) through Lyz2+Ly6C+CD11c- pro-DC3s, whereas DC2s develop from common DC progenitors (CDPs) through CD7+Ly6C+CD11c+ pre-DC2s. Corresponding DC subsets, developmental stages, and lineages exist in humans. These findings reveal DC3 as a DC lineage phenotypically related to but developmentally different from monocytes and DC2s.