Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 4733-4743 |
| Number of pages | 11 |
| Journal | Blood |
| Volume | 120 |
| Issue number | 24 |
| DOIs | |
| Publication status | Published - Dec 6 2012 |
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ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
Cite this
Spi-B is critical for plasmacytoid dendritic cell function and development. / Sasaki, Izumi; Hoshino, Katsuaki; Sugiyama, Takahiro; Yamazaki, Chihiro; Yano, Takahiro; Iizuka, Akihiko; Hemmi, Hiroaki; Tanaka, Takashi; Saito, Masuyoshi; Sugiyama, Masanaka; Fukuda, Yuri; Ohta, Tomokazu; Sato, Katsuaki; Ainai, Akira; Suzuki, Tadaki; Hasegawa, Hideki; Toyama-Sorimachi, Noriko; Kohara, Hiroshi; Nagasawa, Takashi; Kaisho, Tsuneyasu.
In: Blood, Vol. 120, No. 24, 06.12.2012, p. 4733-4743.Research output: Contribution to journal › Article
}
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.
UR - http://www.scopus.com/inward/record.url?scp=84870736373&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870736373&partnerID=8YFLogxK
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 -