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CUTTING EDGE |
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
IFN consensus sequence binding protein (ICSBP/IFN regulatory factor 8) is a hematopoietic cell-specific transcription factor essential for the generation of CD8
+ dendritic cells (DCs). We found that ICSBP-/- mice lack B220+CD11b- plasmacytoid DCs (pDCs) in addition to CD8+ 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 Tefective 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- 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.
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