Cutting edge: IFN consensus sequence binding protein/IFN regulatory factor 8 drives the development of type IIFN-producing plasmacytoid dendritic cells

IFN consensus sequence binding protein (ICSBP/IFN regulatory factor 8) is a hematopoietic cell-specific transcription factor essential for the generation of CD8alpha(+) dendritic cells (DO). We found that ICSBP-/- mice lack B220(+)CD11b(-) plasmacytoid DO (pDCs) in addition to CD8a+ DO. Although ICSBP-/- mice have B220(-)CD11b(+) myeloid DCs (mDCs), they fail to mature upon Toll-like receptors signaling. Accordingly, ICSBP-/- bone marrow progenitor. tor cells were defective in generating pDCs in the fins-like tyrosine kinase 3 ligand-based culture system and mDCs generated in this system were defective in maturation. We demonstrate that introduction of ICSBP rescues the development of pDCs from -/- bone marrow progenitors. ICSBP also restored the ability of both pDcs and mDCs to mature after Toll-like receptor signals. ICSBP restored DCs produced IFN-alpha and IL-12p40 in a DCs subset-selective manner with the amounts comparable to those by +/+ DCs. Together, ICSBP is essential for early pDC development and final maturation of both pDCs, and mDCs.