Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8α+ dendritic cells

By L. Poulin, M. Salio, E. Griessinger, Fernando Anjos-Afonso, L. Craciun, Ji-Li Chen, Anna M. Keller, O. Joffre, S. Zelenay, E. Nye and 7 more. Journal of Experimental Medicine, 2010

716 citations recorded by the source corpus.

In mouse, a subset of dendritic cells (DCs) known as CD8α+ DCs has emerged as an important player in the regulation of T cell responses and a promising target in vaccination strategies. However, translation into clinical protocols has been hampered by the failure to identify CD8α+ DCs in humans. Here, we characterize a population of human DCs that expresses DNGR-1 (CLEC9A) and high levels of BDCA3 and resembles mouse CD8α+ DCs in phenotype and function. We describe the presence of such cells in the spleens of humans and humanized mice and report on a protocol to generate them in vitro. Like mouse CD8α+ DCs, human DNGR-1+ BDCA3hi DCs express Necl2, CD207, BATF3, IRF8, and TLR3, but not CD11b, IRF4, TLR7, or (unlike CD8α+ DCs) TLR9. DNGR-1+ BDCA3hi DCs respond to poly I:C and agonists of TLR8, but not of TLR7, and produce interleukin (IL)-12 when given innate and T cell–derived signals. Notably, DNGR-1+ BDCA3+ DCs from in vitro cultures efficiently internalize material from dead cells and can cross-present exogenous antigens to CD8+ T cells upon treatment with poly I:C. The characterization of human DNGR-1+ BDCA3hi DCs and the ability to grow them in vitro opens the door for exploiting this subset in immunotherapy.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/1e8f308dc5361f83544f757ed626785240ae569c

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In Immunology

1. Florent Ginhoux
2. K. Honda
3. E. Stanley
4. Shizuo Akira
5. R. Medzhitov
6. M. Guilliams

Citations in the corpus

• Human Tissues Contain CD141hi Cross-Presenting Dendritic Cells with Functional Homology to Mouse CD103+ Nonlymphoid Dendritic Cells (2012, background): “CD141hi DCs and blood CD141+ DCs produce very little IL-12 (Jongbloed et al., 2010; Poulin et al., 2010) in contrast to monocyte-derived DCs (Ebner et al., 2001) and mouse cross-presenting DCs (Reis e Sousa et al., 1997).”
• Expansion and activation of CD103+ dendritic cell progenitors at the tumor site enhances tumor responses to therapeutic PD-L1 and BRAF inhibition (2016, neutral): “…CD103+ DCs, human CD141+ DCs express IRF8 and high levels of FLT3 and TLR3, and pIC activation of human CD141+ cells leads to the upregula- tion of PD-L1 (Bogunovic et al., 2011) and to their increased cross-priming of CD8+ T cells (Crozat et al., 2010; Jongbloed et al., 2010; Poulin et al., 2010).”
• Cancer immunotherapy via dendritic cells (2012, neutral): “Human CD141CD1c DCs uniquely express Toll-like receptor (TLR) 3, produce interleukin (IL) 12, and efficiently cross-prime CD8 T cells when activated with poly I:C [17–23].”
• IRF4 Transcription Factor-Dependent CD11b+ Dendritic Cells in Human and Mouse Control Mucosal IL-17 Cytokine Responses (2013, background): “, 2012), similar to blood CD141 DCs (Bachem et al., 2010; Crozat et al., 2010; Poulin et al., 2010).”