Critical roles of interferon regulatory factor 4 in CD11bhighCD8alpha- dendritic cell development

Shoichi Suzuki; Kiri Honma; Toshifumi Matsuyama; Kazuo Suzuki; Kan Toriyama; Ichinose Akitoyo; Kazuo Yamamoto; Takashi Suematsu; Michio Nakamura; Katsuyuki Yui; Atsushi Kumatori

doi:10.1073/pnas.0402139101

Critical roles of interferon regulatory factor 4 in CD11bhighCD8alpha- dendritic cell development

Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8981-6. doi: 10.1073/pnas.0402139101. Epub 2004 Jun 7.

Authors

Shoichi Suzuki¹, Kiri Honma, Toshifumi Matsuyama, Kazuo Suzuki, Kan Toriyama, Ichinose Akitoyo, Kazuo Yamamoto, Takashi Suematsu, Michio Nakamura, Katsuyuki Yui, Atsushi Kumatori

Affiliation

¹ Department of Host-Defense Biochemistry, Institute of Tropical Medicine, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.

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 CD11b(low)CD8alpha(+) conventional dendritic cells (DCs) and plasmacytoid DCs. Here we show that IRF-4 is important for CD11b(high)CD8alpha(-) conventional DCs. The development of CD11b(high) 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(+)CD8alpha(-) DCs, a major subset of CD11b(high) DCs, was severely reduced. IRF-4 and IRF-8 were expressed in the majority of CD11b(high)CD4(+)CD8alpha(-) DCs and CD11b(low)CD8alpha(+) 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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Marrow Cells / metabolism
CD11b Antigen / immunology*
CD4 Antigens / immunology
CD8 Antigens / immunology*
CHO Cells
Cell Culture Techniques / methods
Cell Differentiation
Cricetinae
Cricetulus
DNA-Binding Proteins / deficiency*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / physiology*
Dendritic Cells / cytology*
Dendritic Cells / immunology*
Flow Cytometry
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
Interferon Regulatory Factors
Male
Membrane Proteins / pharmacology
Mice
Mice, Inbred C57BL
Mice, Knockout
Recombinant Proteins
Spleen / cytology
Spleen / immunology
Thymus Gland / cytology
Trans-Activators / deficiency
Trans-Activators / genetics
Trans-Activators / physiology

Substances

CD11b Antigen
CD4 Antigens
CD8 Antigens
DNA-Binding Proteins
Interferon Regulatory Factors
Membrane Proteins
Recombinant Proteins
Trans-Activators
flt3 ligand protein
interferon regulatory factor-4
Granulocyte-Macrophage Colony-Stimulating Factor