Cutting Edge: IFN Consensus Sequence Binding Protein/IFN Regulatory Factor 8 Drives the Development of Type I IFN-Producing Plasmacytoid Dendritic Cells

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摘要：

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 (DCs). We found that ICSBP(-/-) mice lack B220(+)CD11b(-) plasmacytoid DCs (pDCs) in addition to CD8alpha(+) 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-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.

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关键词：

IFN consensus sequence binding protein Dendritic Cells Toll-like receptor 树突细胞

DOI：

10.4049/jimmunol.170.3.1131

被引量：

1001

年份：

2003