What Makes a pDC: Recent Advances in Understanding Plasmacytoid DC Development and Heterogeneity

doi:10.3389/fimmu.2019.01222

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Front Immunol. 2019; 10: 1222.

Published online 2019 May 29. doi: 10.3389/fimmu.2019.01222

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Figure 1

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Converging plasmacytoid dendritic cell differentiation pathways. Plasmacytoid dendritic cells (pDCs) can be derived from both myeloid and lymphoid progenitors. Common DC progenitors (CDPs) arise from lymphoid primed multipotent progenitors (LMPPs) either directly or via macrophage-DC progenitors (MDPs). CDPs contain precursor cells committed to conventional DC (cDC) and plasmacytoid DC fates, and M-CSFR⁻ CDPs have higher pDC potential than M-CSFR⁺ CDPs. A fraction of CDPs can give rise to CCR9^low pDC-like precursor cells and then CCR9^high pDCs in an E2-2 dependent manner. pDC-like cells retain the potential to differentiate into cDCs as well as CCR9^high mature pDCs. Inhibitor of DNA binding 2 (Id2), which inhibits E2-2 activity, needs to be suppressed to allow pDC differentiation. pDCs are also generated via the lymphoid pathway, from IL-7R⁺ lymphoid progenitors (LPs) which give rise to Ly-6D single positive (SP) LP and subsequently to Ly-6D Siglec-H double positive (DP) pre-pDC, terminally committed to the pDC fate.