Transcriptional and functional analysis of CD1c+ human dendritic cells identifies a CD163+ subset priming CD8+CD103+ T cells [Breast_iLN]
Dendritic cells (DC) are antigen presenting cells controlling T cell activation. In human, the diversity, ontogeny and functional capabilities of DC subsets are not fully understood. Here, we identified circulating CD88-CD1c+CD163+ DC (termed as DC3) as an immediate precursor of inflammatory CD88-CD14+CD1c+CD163+FceRI+ DC. DC3 develop via a specific pathway activated by GM-CSF, independent from the cDC-restricted (CDP) and monocyte-restricted (cMoP) progenitors. As classical DC, but unlike monocytes, DC3 drove the activation of naïve T cells. In vitro, DC3 displayed a distinctive ability to prime CD8+ T cells expressing a tissue-homing signature and the epithelial homing alpha-E integrin (CD103) through transforming growth factor-b (TGF-ß) signaling. In vivo, DC3 infiltrated luminal breast cancer primary tumors and DC3 infiltration correlated positively with CD8+CD103+CD69+ tissue-resident memory T cells. Altogether, these findings define DC3 as a lineage of inflammatory DC endowed with a strong potential to regulate tumor immunity. Overall design: Tumor-draining lymph nodes (tdLN) and primary tumors were collected and processed within few hours after the primary surgery. CD11c+HLADR+CD14-CD1a-CD206-CD1c+,  CD11c+HLADR+CD1a-CD1c-CD14+ and CD11c+HLADR+CD1a-CD1c+CD14+ cells were sorted in triplicates with up to 1000 cells per sample.