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. |