Transcriptional and Functional Analysis of CD1c+ Human Dendritic Cells Identifies a CD163+ Subset Priming CD8+CD103+ T Cells
Transcriptional and Functional Analysis of CD1c+ Human Dendritic Cells Identifies a CD163+ Subset Priming CD8+CD103+ T Cells
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DOI：
10.1016/j.immuni.2020.06.002
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发表时间：
2020-08-18
期刊：
影响因子：
32.4
通讯作者：
Guermonprez, Pierre
中科院分区：
文献类型：
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作者：
Bourdely, Pierre;Anselmi, Giorgio;Guermonprez, Pierre
树突状细胞(DC)是控制T细胞活化的抗原提呈细胞。在人类中，DC亚群的多样性、个体发育和功能还没有完全被理解。在这里，我们发现循环中的CD88(-)CD1c(+)CD163(+)DC(称为DC3s)是炎症性CD88(-)CD14(+)CD1c(+)CD163(+)Fc epsilon RI+DC的直接前体。DC3通过GM-CSF激活的特定途径发展，不依赖于CDC限制性(CDP)和单核细胞限制性(CMoP)祖细胞。与经典的DC类似，但与单核细胞不同，DC3s推动了原始T细胞的激活。在体外，DC3s表现出独特的能力，通过转化生长因子β信号激活表达组织归巢信号的CD8(+)T细胞和上皮归巢整合素α-E整合素(CD103)。在体内，DC3s浸润腔内乳腺癌原发灶，DC3浸润率与CD8(+)CD103(+)CD69(+)组织驻留记忆T细胞呈正相关。综上所述，这些发现将DC3定义为具有调节肿瘤免疫的强大潜力的炎症性DC谱系。
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(+)Fc epsilon RI+ 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 beta (TGF-beta) 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.