Critical roles of interferon regulatory factor 4 in CD11bhighCD8alpha- dendritic cell development.
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.
Suzuki
Shoichi
S
Department of Host-Defense Biochemistry, Institute of Tropical Medicine, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Honma
Kiri
K
Matsuyama
Toshifumi
T
Suzuki
Kazuo
K
Toriyama
Kan
K
Akitoyo
Ichinose
I
Yamamoto
Kazuo
K
Suematsu
Takashi
T
Nakamura
Michio
M
Yui
Katsuyuki
K
Kumatori
Atsushi
A
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology*; D016466:CHO Cells; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D006224:Cricetinae; D003412:Cricetulus; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D050835:Interferon Regulatory Factors; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011994:Recombinant Proteins; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D000099218:Interferon Regulatory Factor-4
D039481:CD11b Antigen; D015704:CD4 Antigens; D016827:CD8 Antigens; D004268:DNA-Binding Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D050835:Interferon Regulatory Factors; D008565:Membrane Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D000099218:Interferon Regulatory Factor-4; C084881:flt3 ligand protein