title: Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8alpha+ dendritic cells.
abstract: 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.
authors.affiliation: Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK.
authors.forename: Lionel Franz
authors.initials: LF
authors.lastname: Poulin
authors.forename: Mariolina
authors.initials: M
authors.lastname: Salio
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Griessinger
authors.forename: Fernando
authors.initials: F
authors.lastname: Anjos-Afonso
authors.forename: Ligia
authors.initials: L
authors.lastname: Craciun
authors.forename: Ji-Li
authors.initials: JL
authors.lastname: Chen
authors.forename: Anna M
authors.initials: AM
authors.lastname: Keller
authors.forename: Olivier
authors.initials: O
authors.lastname: Joffre
authors.forename: Santiago
authors.initials: S
authors.lastname: Zelenay
authors.forename: Emma
authors.initials: E
authors.lastname: Nye
authors.forename: Alain
authors.initials: A
authors.lastname: Le Moine
authors.forename: Florence
authors.initials: F
authors.lastname: Faure
authors.forename: Vincent
authors.initials: V
authors.lastname: Donckier
authors.forename: David
authors.initials: D
authors.lastname: Sancho
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnet
authors.forename: Caetano
authors.initials: C
authors.lastname: Reis e Sousa
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D045142:Cross-Priming / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D018664:Interleukin-12 / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000378:metabolism*; D051379:Mice; D010641:Phenotype; D011070:Poly I-C / Q000494:pharmacology; D011975:Receptors, Mitogen / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018180:Thrombomodulin; D051193:Toll-Like Receptors / Q000819:agonists
chemical_list: D000954:Antigens, Surface; C530206:CLEC9a protein, human; D037181:Lectins, C-Type; D011975:Receptors, Mitogen; C546931:THBD protein, human; D018180:Thrombomodulin; D051193:Toll-Like Receptors; D018664:Interleukin-12; D011070:Poly I-C