Final Report Summary - CD8DC FUNCTIONS (DNRG-1 as a marker to develop better models for characterising human and mouse dendritic subsets and for analysing their functional role in vivo)
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 characterise 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 humanised 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 polyI: 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 internalise material from dead cells and can cross-present exogenous antigens to CD8+ T cells upon treatment with poly I: C. The characterisation of human DNGR-1+
BDCA3hi DCs and the ability to grow them in vitro opens the door for exploiting this subset in immunotherapy.
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 polyI: 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 internalise material from dead cells and can cross-present exogenous antigens to CD8+ T cells upon treatment with poly I: C. The characterisation of human DNGR-1+
BDCA3hi DCs and the ability to grow them in vitro opens the door for exploiting this subset in immunotherapy.