Abstract
Dendritic cells (DCs), including conventional DCs (cDCs) and plasmacytoid DCs (pDCs) are critical for initiating and controlling the immune response. However, study of DC, particularly pDC, function is hampered by their low frequency in lymphoid organs, and existing methods for in vitro DC generation preferentially favor the production of cDCs over pDCs. Here, we demonstrated that pDCs could be efficiently generated in vitro from common lymphoid progenitors (CLPs) using Flt3 ligand (FL) in three different culture systems, namely feeder-free, BM-feeder and AC-6-feeder. This was in stark contrast to common DC progenitors (CDPs), in which cDCs were prominently generated under the same conditions. Moreover, the efficiency and function of pDCs generated from these three systems varied. While AC-6 system showed the greatest ability to support pDC development from CLPs, BM-feeder system was able to develop pDCs with better functionality. pDCs could also be expanded in vivo using hydrodynamic gene transfer of FL, which was further enhanced by the combined treatment of FL and IFN-α. Interestingly, IFN-α selectively promoted the proliferation of CLPs and not CDPs, which might contribute to enhanced pDC development. Together, we have defined conditions for in vitro and in vivo generation of pDCs, which may be useful for investigating the biology of pDCs.
Highlights
Plasmacytoid Dendritic cells (DCs) are innate immune cells that are capable of producing large quantities of type I interferon (IFN-I) upon stimulation and activation [1, 2]
We have previously shown that common lymphoid progenitors (CLPs) could preferentially develop plasmacytoid DCs (pDCs) in vitro [8]
We examined their pDC potential in FF system. They generated higher percentages of pDCs than did common DC progenitors (CDPs), their pDC potential was still lower than those of CLPs (S2 Fig). These results suggest that CLPs develop more pDCs than conventional DCs (cDCs) in vitro and that they have a greater pDC potential than do CDPs and M-CSFR- DC progenitors
Summary
Plasmacytoid DC (pDCs) are innate immune cells that are capable of producing large quantities of type I interferon (IFN-I) upon stimulation and activation [1, 2]. The frequencies of pDCs are low and their life span is short compared to other immune cells. They are constantly replenished from their progenitors to maintain their homeostasis at steady state [3]. Progenitors of both myeloid and lymphoid lineages are able to generate pDCs [4, 5]. We and others showed that CLPs had the ability to generate more pDCs than cDCs [6, 8]. The developmental origins of pDCs are still not completely understood
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