Spi-B is critical for plasmacytoid dendritic cell function and development
| Autor: | Tomokazu Ohta, Hiroshi Kohara, Katsuaki Sato, Takashi Tanaka, Katsuaki Hoshino, Akira Ainai, Yuri Fukuda, Takashi Nagasawa, Takahiro Sugiyama, Hiroaki Hemmi, Tsuneyasu Kaisho, Masanaka Sugiyama, Takahiro Yano, Hideki Hasegawa, Izumi Sasaki, Chihiro Yamazaki, Masuyoshi Saito, Tadaki Suzuki, Noriko Toyama-Sorimachi, Akihiko Iizuka |
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| Rok vydání: | 2012 |
| Předmět: |
Transcriptional Activation
Immunology Molecular Sequence Data Bone Marrow Cells Plasmacytoid dendritic cell Biology Biochemistry Flow cytometry Mice medicine Animals Humans Promoter Regions Genetic Transcription factor Oligonucleotide Array Sequence Analysis Mice Knockout medicine.diagnostic_test Base Sequence Proto-Oncogene Proteins c-ets Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling HEK 293 cells TLR9 hemic and immune systems Promoter Cell Biology Hematology TLR7 Dendritic cell Dendritic Cells Flow Cytometry Cell biology Mice Inbred C57BL HEK293 Cells Toll-Like Receptor 7 Toll-Like Receptor 9 Interferon Type I Mutation |
| Zdroj: | Blood. 120(24) |
| ISSN: | 1528-0020 |
| Popis: | Plasmacytoid dendritic cells (pDCs), originating from hematopoietic progenitor cells in the BM, are a unique dendritic cell subset that can produce large amounts of type I IFNs by signaling through the nucleic acid–sensing TLR7 and TLR9 (TLR7/9). The molecular mechanisms for pDC function and development remain largely unknown. In the present study, we focused on an Ets family transcription factor, Spi-B, that is highly expressed in pDCs. Spi-B could transactivate the type I IFN promoters in synergy with IFN regulatory factor 7 (IRF-7), which is an essential transcription factor for TLR7/9-induced type I IFN production in pDCs. Spi-B–deficient pDCs and mice showed defects in TLR7/9-induced type I IFN production. Furthermore, in Spi-B–deficient mice, BM pDCs were decreased and showed attenuated expression of a set of pDC-specific genes whereas peripheral pDCs were increased; this uneven distribution was likely because of defective retainment of mature nondividing pDCs in the BM. The expression pattern of cell-surface molecules in Spi-B–deficient mice indicated the involvement of Spi-B in pDC development. The developmental defects of pDCs in Spi-B–deficient mice were more prominent in the BM than in the peripheral lymphoid organs and were intrinsic to pDCs. We conclude that Spi-B plays critical roles in pDC function and development. |
| Databáze: | OpenAIRE |
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