The superiority of dendritic cells (DCs) as antigen-presenting cells has been 
exploited in numerous clinical trials, where generally monocyte-derived DCs 
(Mo-DCs) are injected to induce immunity in patients with cancer or infectious 
diseases. Despite promising expansion of antigen-specific T cells, the clinical 
responses following vaccination have been limited, indicating that further 
improvements of DC vaccine potency are necessary. Pre-clinical studies suggest 
that vaccination with combination of primary DC subsets, such as myeloid and 
plasmacytoid blood DCs (mDCs and pDCs, respectively), may result in stronger 
clinical responses. However, it is a challenge to obtain high enough numbers of 
primary DCs for immunotherapy, since their frequency in blood is very low. We 
therefore explored the possibility to generate them from hematopoietic 
progenitor cells (HPCs). Here, we show that by inhibiting the aryl hydrocarbon 
receptor with its antagonist StemRegenin 1 (SR1), clinical-scale numbers of 
functional BDCA2(+)BDCA4(+) pDCs, BDCA1(+) mDCs, and BDCA3(+)DNGR1(+) mDCs can 
be efficiently generated from human CD34(+) HPCs. The ex vivo-generated DCs were 
phenotypically and functionally comparable to peripheral blood DCs. They 
secreted high levels of pro-inflammatory cytokines such as interferon (IFN)-α, 
interleukin (IL)-12, and tumor necrosis factor (TNF)-α and upregulated 
co-stimulatory molecules and maturation markers following stimulation with 
Toll-like receptor (TLR) ligands. Further, they induced potent allogeneic T-cell 
responses and activated antigen-experienced T cells. These findings demonstrate 
that SR1 can be exploited to generate high numbers of functional pDCs and mDCs 
from CD34(+) HPCs, providing an alternative option to Mo-DCs for immunotherapy 
of patients with cancer or infections.