Open AccessCutting Edge: IFN Consensus Sequence Binding Protein/IFN Regulatory Factor 8 Drives the Development of Type I IFN-Producing Plasmacytoid Dendritic Cells
Author(s) -
Hideki Tsujimura,
Tomohide Tamura,
Keiko Ozato
Publication year - 2003
Publication title -
the journal of immunology/the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.170.3.1131
Subject(s) - haematopoiesis , biology , progenitor cell , plasmacytoid dendritic cell , myeloid , dendritic cell , cd8 , immunology , bone marrow , irf8 , transcription factor , microbiology and biotechnology , cancer research , stem cell , immune system , gene , genetics
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.