Cutting edge: IFN consensus sequence binding protein/IFN regulatory factor 8 drives the development of type I IFN-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 CD8 alpha(+) dendritic cells (DCs). We found that ICSBP(-/-) mice lack B220(+)CD11b(-) plasmacytoid DCs (pDCs) in addition to CD8 alpha(+) DCs. Although ICSBP(-/-) mice have B220(-)CD11b(+) myeloid DCs (mDCs), they fail to mature upon Toll-like receptor signaling. Accordingly, ICSBP(-/-) bone marrow progenitor cells were defective in generating pDCs in the fms-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 DC 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.