Spi-B is critical for plasmacytoid dendritic cell function and development

Izumi Sasaki, Katsuaki Hoshino, Takahiro Sugiyama, Chihiro Yamazaki, Takahiro Yano, Akihiko Iizuka, Hiroaki Hemmi, Takashi Tanaka, Masuyoshi Saito, Masanaka Sugiyama, Yuri Fukuda, Tomokazu Ohta, Katsuaki Sato, Akira Ainai, Tadaki Suzuki, Hideki Hasegawa, Noriko Toyama-Sorimachi, Hiroshi Kohara, Takashi Nagasawa, Tsuneyasu Kaisho

Research output: Contribution to journalArticle

40 Citations (Scopus)

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 languageEnglish
Pages (from-to)4733-4743
Number of pages11
JournalBlood
Volume120
Issue number24
DOIs
Publication statusPublished - Dec 6 2012

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Sasaki, I., Hoshino, K., Sugiyama, T., Yamazaki, C., Yano, T., Iizuka, A., Hemmi, H., Tanaka, T., Saito, M., Sugiyama, M., Fukuda, Y., Ohta, T., Sato, K., Ainai, A., Suzuki, T., Hasegawa, H., Toyama-Sorimachi, N., Kohara, H., Nagasawa, T., & Kaisho, T. (2012). Spi-B is critical for plasmacytoid dendritic cell function and development. Blood, 120(24), 4733-4743. https://doi.org/10.1182/blood-2012-06-436527