关键词： DC progenitors DC3s T(RM) cDC2s conventional DCs inflammatory DCs monocytes mononuclear phagocytes

Mesh ： Animals Antigens, CD / metabolism Antigens, CD1 / metabolism Antigens, Differentiation, Myelomonocytic / metabolism Breast Neoplasms / immunology CD8 Antigens / metabolism CD8-Positive T-Lymphocytes / cytology immunology Cell Differentiation / immunology Cell Line, Tumor Dendritic Cells / immunology Glycoproteins / metabolism Granulocyte-Macrophage Colony-Stimulating Factor / metabolism Humans Integrin alpha Chains / metabolism Lymphocyte Activation / immunology Mice Mice, Inbred NOD Receptors, Cell Surface / metabolism Transforming Growth Factor beta1 / metabolism fms-Like Tyrosine Kinase 3 / metabolism

来  源：   DOI：10.1016/j.immuni.2020.06.002   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
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.
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