Critical roles of interferon regulatory factor 4 in CD11bhighCD8α– dendritic cell development
- Shoichi Suzuki*,
- Kiri Honma†,
- Toshifumi Matsuyama‡,§,
- Kazuo Suzuki¶,
- Kan Toriyama∥,
- Ichinose Akitoyo**,
- Kazuo Yamamoto‡,
- Takashi Suematsu††,
- Michio Nakamura*,
- Katsuyuki Yui†, and
- Atsushi Kumatori*
- Departments of *Host-Defense Biochemistry and ∥Pathology, **Central Laboratory, Institute of Tropical Medicine, †Division of Immunology, Department of Translational Medical Sciences, ‡Department of Molecular Microbiology and Immunology, and ††Electron Microscope Center, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; and ¶Laboratory of Biodefense, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
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Edited by Ralph M. Steinman, The Rockefeller University, New York, NY, and approved April 27, 2004 (received for review March 29, 2004)
Abstract
IFN regulatory factors (IRFs) are a family of transcription factors that play an essential role in the homeostasis and function of immune systems. Recent studies indicated that IRF-8 is critical for the development of CD11blowCD8α+ conventional dendritic cells (DCs) and plasmacytoid DCs. Here we show that IRF-4 is important for CD11bhighCD8α– conventional DCs. The development of CD11bhigh DCs from bone marrow of IRF-4–/– mice was severely impaired in two culture systems supplemented with either GM-CSF or Flt3-ligand. In the IRF-4–/– spleen, the number of CD4+CD8α– DCs, a major subset of CD11bhigh DCs, was severely reduced. IRF-4 and IRF-8 were expressed in the majority of CD11bhighCD4+CD8α– DCs and CD11blowCD8α+ DCs, respectively, in a mutually exclusive manner. These results imply that IRF-4 and IRF-8 selectively play critical roles in the development of the DC subsets that express them.
Footnotes
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↵ § To whom correspondence should be addressed. E-mail: tosim{at}net.nagasaki-u.ac.jp.
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This paper was submitted directly (Track II) to the PNAS office.
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Abbreviations: DC, dendritic cell; BM, bone marrow; Flt3L, Flt3 ligand; GM-CSF, granulocyte–macrophage colony-stimulating factor; LPS, lipopolysaccharide; IRF, IFN-regulatory factor; PE, phycoerythrin; PerCP, peridinin chlorophyll-α protein; NPTII, neomycin phosphotransferase II; OVA, ovalbumin; MHC-II, MHC class II; NK, natural killer.
- Copyright © 2004, The National Academy of Sciences
