Dendritic cells (DCs) are antigen-presenting cells controlling T cell activation. In humans, the diversity, ontogeny, and functional capabilities of DC subsets are not fully understood. Here, we identified circulating CD88⁻CD1c⁺CD163⁺ DCs (called DC3s) as immediate precursors of inflammatory CD88⁻CD14⁺CD1c⁺CD163⁺FcεRI⁺ DCs. DC3s develop via a specific pathway activated by GM-CSF, independent of cDC-restricted (CDP) and monocyte-restricted (cMoP) progenitors. Like classical DCs but unlike monocytes, DC3s drove activation of naive T cells. In vitro, DC3s 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 β (TGF-β) signaling. In vivo, DC3s infiltrated luminal breast cancer primary tumors, and DC3 infiltration correlated positively with CD8⁺CD103⁺CD69⁺ tissue-resident memory T cells. Together, these findings define DC3s as a lineage of inflammatory DCs endowed with a strong potential to regulate tumor immunity.

树突状细胞 (DC) 是控制 T 细胞激活的抗原呈递细胞。在人类中，DC 亚群的多样性、个体发育和功能能力尚未完全了解。在这里，我们确定循环 CD88 ⁻ CD1c ⁺ CD163 ⁺ DC（称为 DC3）是炎症性 CD88 ⁻ CD14 ⁺ CD1c ⁺ CD163 ⁺ FcεRI ⁺ DC 的直接前体。 DC3 通过 GM-CSF 激活的特定途径发育，独立于 cDC 限制性 (CDP) 和单核细胞限制性 (cMoP) 祖细胞。与经典 DC 一样，但与单核细胞不同，DC3 驱动初始 T 细胞的激活。在体外，DC3表现出独特的能力，通过转化生长因子β（TGF-β）信号传导来启动表达组织归巢信号和上皮归巢α-E整合素（CD103）的CD8 ⁺ T细胞。在体内，DC3浸润乳腺癌原发肿瘤的管腔，并且DC3浸润与CD8 ⁺ CD103 ⁺ CD69 ⁺组织驻留记忆T细胞呈正相关。总之，这些发现将 DC3 定义为炎症性 DC 的谱系，具有调节肿瘤免疫的强大潜力。