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Publication : Progenitors of distinct lineages shape the diversity of mature type 2 conventional dendritic cells.

First Author  Rodrigues PF Year  2024
Journal  Immunity PubMed ID  38821051
Mgi Jnum  J:349926 Mgi Id  MGI:7660354
Doi  10.1016/j.immuni.2024.05.007 Citation  Rodrigues PF, et al. (2024) Progenitors of distinct lineages shape the diversity of mature type 2 conventional dendritic cells. Immunity
abstractText  Conventional dendritic cells (cDC) are antigen-presenting cells comprising cDC1 and cDC2, responsible for priming naive CD8(+) and CD4(+) T cells, respectively. Recent studies have unveiled cDC2 heterogeneity and identified various cDC2 progenitors beyond the common DC progenitor (CDP), hinting at distinct cDC2 lineages. By generating Cd300c(iCre-hCD2)R26(tdTomato) reporter mice, we identified a bone marrow pro-cDC2 progenitor exclusively generating cDC2 in vitro and in vivo. Single-cell analyses and multiparametric flow cytometry demonstrated that pro-cDC2 encompasses myeloid-derived pre-cDC2 and lymphoid-derived plasmacytoid DC (pDC)-like precursors differentiating into a transcriptionally convergent cDC2 phenotype. Cd300c-traced cDC2 had distinct transcriptomic profiles, phenotypes, and tissue distributions compared with Ms4a3(Cre)R26(tdTomato) lineage-traced DC3, a monocyte-DC progenitor (MDP)-derived subset that bypasses CDP. Mice with reduced Cd300c-traced cDC2 showed impaired humoral responses to T cell-dependent antigens. We conclude that progenitors of distinct lineages shape the diversity of mature cDC2 across tissues. Thus, ontogenesis may impact tissue immune responses.
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