TY - JOUR
T1 - Spi-B is critical for plasmacytoid dendritic cell function and development
AU - Sasaki, Izumi
AU - Hoshino, Katsuaki
AU - Sugiyama, Takahiro
AU - Yamazaki, Chihiro
AU - Yano, Takahiro
AU - Iizuka, Akihiko
AU - Hemmi, Hiroaki
AU - Tanaka, Takashi
AU - Saito, Masuyoshi
AU - Sugiyama, Masanaka
AU - Fukuda, Yuri
AU - Ohta, Tomokazu
AU - Sato, Katsuaki
AU - Ainai, Akira
AU - Suzuki, Tadaki
AU - Hasegawa, Hideki
AU - Toyama-Sorimachi, Noriko
AU - Kohara, Hiroshi
AU - Nagasawa, Takashi
AU - Kaisho, Tsuneyasu
PY - 2012/12/6
Y1 - 2012/12/6
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2012-06-436527
DO - 10.1182/blood-2012-06-436527
M3 - Article
C2 - 23065153
AN - SCOPUS:84870736373
VL - 120
SP - 4733
EP - 4743
JO - Blood
JF - Blood
SN - 0006-4971
IS - 24
ER -