Spi-B is critical for plasmacytoid dendritic cell function and development.
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.
Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Kanagawa, Japan.
Izumi
I
Sasaki
Katsuaki
K
Hoshino
Takahiro
T
Sugiyama
Chihiro
C
Yamazaki
Takahiro
T
Yano
Akihiko
A
Iizuka
Hiroaki
H
Hemmi
Takashi
T
Tanaka
Masuyoshi
M
Saito
Masanaka
M
Sugiyama
Yuri
Y
Fukuda
Tomokazu
T
Ohta
Katsuaki
K
Sato
Akira
A
Ainai
Tadaki
T
Suzuki
Hideki
H
Hasegawa
Noriko
N
Toyama-Sorimachi
Hiroshi
H
Kohara
Takashi
T
Nagasawa
Tsuneyasu
T
Kaisho
D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000502:physiology; D003713:Dendritic Cells / Q000378:metabolism* / Q000502:physiology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000502:physiology; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000502:physiology; D015533:Transcriptional Activation
D007370:Interferon Type I; D050783:Proto-Oncogene Proteins c-ets; C514177:Spi-B protein, mouse; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9