PMID- 15004277
OWN - NLM
STAT- MEDLINE
DCOM- 20040423
LR  - 20240411
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 101
IP  - 11
DP  - 2004 Mar 16
TI  - Defective development of splenic and epidermal CD4+ dendritic cells in mice 
      deficient for IFN regulatory factor-2.
PG  - 3909-14
AB  - Dendritic cells (DCs) play important roles in the initiation and regulation of 
      immune responses. Although several subsets of DCs were identified according to 
      their expression of surface molecules such as CD4, CD8, and CD11b, the regulatory 
      mechanism for the development and homeostasis of these DC subsets remains 
      unclear. Here we show that mice lacking IFN regulatory factor-2 (IRF-2(-/-) mice) 
      exhibited a marked and selective defect in splenic CD4(+)CD11b(+)DCs, instead of 
      CD8 alpha(+)CD11b(-)DCs that were reported to be missing in mice lacking the 
      related transcription factor IRF-8. Furthermore, the numbers of epidermal 
      Langerhans cells in IRF-2(-/-) mice were reduced at least in part because of the 
      lack of the CD4(+)CD11b(+) subset. Studies with radiation bone marrow chimeras as 
      well as in vitro retrovirus-mediated gene transduction showed that IRF-2 was 
      required cell-autonomously for the development of myeloid-related DCs. Notably, 
      these abnormalities in DCs diminished in mice lacking both IRF-2 and the 
      IFN-alpha/beta receptor, indicating that IRF-2 acted through negatively 
      regulating IFN-alpha/beta signals. In contrast, natural killer cells still showed 
      developmental arrest in these double mutant mice, indicating that the mode of 
      action of IRF-2 for CD4(+)DC development is distinct from that for natural killer 
      cell development. Our current findings thus pointed to a previously unknown 
      unique cell-type-selective multimode function of IRF-2 in the regulation of 
      lymphohematopoiesis.
FAU - Ichikawa, Eri
AU  - Ichikawa E
AD  - Department of Immunology and Infectious Diseases, Shinshu University Graduate 
      School of Medicine, Asahi 3-1-1, Matsumoto, Nagano 390-8621, Japan.
FAU - Hida, Shigeaki
AU  - Hida S
FAU - Omatsu, Yoshiki
AU  - Omatsu Y
FAU - Shimoyama, Susumu
AU  - Shimoyama S
FAU - Takahara, Kazuhiko
AU  - Takahara K
FAU - Miyagawa, Shinichi
AU  - Miyagawa S
FAU - Inaba, Kayo
AU  - Inaba K
FAU - Taki, Shinsuke
AU  - Taki S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040302
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (CD11b Antigen)
RN  - 0 (CD4 Antigens)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interferon Regulatory Factor-2)
RN  - 0 (Irf2 protein, mouse)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/metabolism
MH  - CD11b Antigen/metabolism
MH  - CD4 Antigens/*metabolism
MH  - Cell Differentiation/physiology
MH  - DNA-Binding Proteins/*deficiency/genetics/metabolism
MH  - Dendritic Cells/*metabolism
MH  - Epidermis/*metabolism
MH  - Interferon Regulatory Factor-2
MH  - Mice
MH  - Mice, Knockout
MH  - *Repressor Proteins
MH  - Spleen/*metabolism
MH  - *Transcription Factors
PMC - PMC374343
EDAT- 2004/03/09 05:00
MHDA- 2004/04/24 05:00
PMCR- 2004/09/16
CRDT- 2004/03/09 05:00
PHST- 2004/03/09 05:00 [pubmed]
PHST- 2004/04/24 05:00 [medline]
PHST- 2004/03/09 05:00 [entrez]
PHST- 2004/09/16 00:00 [pmc-release]
AID - 0400610101 [pii]
AID - 1013909 [pii]
AID - 10.1073/pnas.0400610101 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3909-14. doi: 
      10.1073/pnas.0400610101. Epub 2004 Mar 2.