Plasmacytoid dendritic cells: recent progress and open questions

Abstract

Plasmacytoid dendritic cells (pDCs) are specialized in rapid and massive secretion of type I interferon (IFN-α/β) in response to foreign nucleic acids. Combined with their antigen presentation capacity, this powerful functionality enables pDCs to orchestrate innate and adaptive immune responses. pDCs combine features of both lymphocytes and classical dendritic cells and display unique molecular adaptations to nucleic acid sensing and IFN production. In the decade since the identification of the pDC as a distinct immune cell type, our understanding of its molecular underpinnings and role in immunity has progressed rapidly. Here we review select aspects of pDC biology including cell fate establishment and plasticity, specific molecular mechanisms of pDC function, and the role of pDCs in T cell responses, antiviral immunity, and autoimmune diseases. Important unresolved questions remain in these areas, promising exciting times in pDC research for years to come.

Figure 1

The proposed scheme of pDC development and relationship with cDCs. pDCs develop in the bone marrow from a continuum of Flt3⁺ c-Kit^low progenitors including lymphoid progenitors (dark gray) and common DC progenitors (CDPs, light blue). The development proceeds through the putative committed pDC progenitor (dashed magenta) and immature pDCs in the bone marrow toward the mature peripheral pDCs. The CDP gives rise to peripheral cDCs (dark blue), whereas immature bone marrow pDCs can differentiate into CD8 cDCs upon virus-induced activation. The alternative CD8⁺ DC ( purple) develops from pDC progenitors in the steady state; similar cells can be generated from mature pDCs after induced E2–2 deletion and possibly upon activation. The inferred relative amounts of E protein E2–2 and its inhibitor Id2 are indicated for each cell type.