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.
Tsujimura
Hideki
H
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Tamura
Tomohiko
T
Ozato
Keiko
K
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016384:Consensus Sequence; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D050835:Interferon Regulatory Factors; D007370:Interferon Type I / Q000096:biosynthesis*; D016898:Interferon-alpha / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40; D051379:Mice; D018345:Mice, Knockout; D010950:Plasma Cells / Q000166:cytology* / Q000378:metabolism*; D021122:Protein Subunits / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D000099185:Interferon Regulatory Factor-8
D000949:Histocompatibility Antigens Class II; D050835:Interferon Regulatory Factors; D007370:Interferon Type I; D016898:Interferon-alpha; D018664:Interleukin-12; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D011948:Receptors, Antigen, T-Cell; D012097:Repressor Proteins; D000099185:Interferon Regulatory Factor-8