Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8α+ dendritic cells
Authors list
Lionel Franz Poulin Mariolina Salio Emmanuel Griessinger Fernando Anjos-Afonso Ligia Craciun Ji-Li Chen Anna M Keller Olivier Joffre Santiago Zelenay Emma Nye Alain Le Moine Florence Faure Vincent Donckier David Sancho Vincenzo Cerundolo Dominique Bonnet Caetano Reis e SousaAbstract
In mouse, a subset of dendritic cells (DCs) known as CD8alpha+ 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 CD8alpha+ DCs in humans. Here, we characterize a population of human DCs that expresses DNGR-1 (CLEC9A) and high levels of BDCA3 and resembles mouse CD8alpha+ 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 CD8alpha+ DCs, human DNGR-1+ BDCA3hi DCs express Necl2, CD207, BATF3, IRF8, and TLR3, but not CD11b, IRF4, TLR7, or (unlike CD8alpha+ 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.
Journal details
Journal Journal of Experimental Medicine
Volume 207
Issue number 6
Pages 1261-1271
Publication date
Full text links
Publisher website (DOI) 10.1084/jem.20092618
Europe PubMed Central 20479117
Pubmed 20479117
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