Transcriptional and Functional Analysis of CD1c+ Human Dendritic Cells Identifies a CD163+ Subset Priming CD8+CD103+ T Cells

被引:233
作者
Bourdely, Pierre [1 ,2 ]
Anselmi, Giorgio [1 ,2 ]
Vaivode, Kristine [1 ,2 ]
Ramos, Rodrigo Nalio [3 ]
Missolo-Koussou, Yoann [3 ]
Hidalgo, Sofia [3 ,4 ]
Tosselo, Jimena [3 ]
Nunez, Nicolas [3 ]
Richer, Wilfrid [3 ]
Vincent-Salomon, Anne [5 ]
Saxena, Alka [6 ,7 ]
Wood, Kristie [6 ,7 ]
Lladser, Alvaro [4 ,8 ]
Piaggio, Eliane [3 ]
Helft, Julie [3 ]
Guermonprez, Pierre [1 ,2 ,9 ]
机构
[1] Kings Coll London, Sch Immunol & Microbial Sci, Peter Gorer Dept Immunobiol, Ctr Inflammat Biol & Canc Immunol, London, England
[2] Kings Coll London, Canc Res UK Kings Hlth Partner Canc Ctr, London, England
[3] PSL Res Univ, Inst Curie, Translat Immunotherapy Team, INSERM,Res Ctr,U392, Paris, France
[4] Fdn Ciencia & Vida, Lab Immunooncol, Santiago, Chile
[5] PSL Res Univ, Inst Curie, Dept Biopathol, Paris, France
[6] Guys & St Thomas Hosp, Natl Inst Hlth Res, Biomed Res Ctr, London, England
[7] Kings Coll London, London, England
[8] Univ San Sebastian, Fac Med & Ciencia, Santiago, Chile
[9] Univ Paris, CNRS, Ctr Inflammat Res, INSERM1149,ERL8252, Paris, France
基金
英国国家替代、减少和改良动物研究中心; 英国生物技术与生命科学研究理事会;
关键词
COLONY-STIMULATING FACTOR; MONOCYTE DIFFERENTIATION; GENE-EXPRESSION; GROWTH-FACTOR; FLT3; LIGAND; PROGENITOR; RESIDENT; INTERLEUKIN-4; HETEROGENEITY; MACROPHAGES;
D O I
10.1016/j.immuni.2020.06.002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:335 / +
页数:26
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