2004 Fiscal Year Final Research Report Summary
Gene Expression in Immunological Tolerance and Immune Dysfunctions Caused by Its Disturbance
| Project/Area Number |
15390159
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Shinshu University |
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Principal Investigator |
TAKI Shinsuke Shinshu University, 大学院・医学研究科, 教授 (50262027)
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| Co-Investigator(Kenkyū-buntansha) |
HIDA Shigeaki Shinshu University, Graduate School of Medicine, Department of Immunology and Infectious Diseases, Research Assistant, 大学院・医学研究科, 助手 (10345762)
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| Project Period (FY) |
2003 – 2004
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| Keywords | dendritic cells / NK cells / subset / transcription factors / IRF-2 / interferon / cell differentiation / knockout mice |
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| Research Abstract |
In this study, we have investigated the mechanisms for the immunological abnormalities that had been observed in mice lacking the transcription factor interferon regulatory factor-2 (IRF-2). First, we found that the subset of dendritic cells (DC) bearing CD4 were greatly reduced compared with those in control mice in the spleen and epidermis in these mice. Such a reduction appeared to be due to cell intrinsic defect of IRF-2 in bone marrow cells as indicated in radiation bone marrow (BM) chimeras. Notably, type I interferon signaling were indispensable for the DC phenotype as double mutant mice lacking both IRF-2 and the type I interferon receptor did not show such a phenotype, suggesting that IRF-2 is important for repressing interferon signals, thereby allowing CD4+ DC subset to develop. In these double mutant mice, the skin inflammation developing spontaneously in IRF-2-deficient mice was no longer observed. These observations pointed to an interesting possibility that the abnormali
… More
ty in CD4+ DC subset might contribute to the skin pathogenesis. Furthermore, with respect to another immunological abnormality in IRF-2-deficient mice, NK cell deficiency, we showed that IRF-2 functioned at a late step during NK cell development, and only immature NK cells were remaining in the BM in IRF-2-deficient mice. Curiously, residual NK cells in the spleen were even less mature than those in the bone marrow in these mice as judged from the expression patterns of Ly49 and other cell surface markers. This differential NK cell maturation arrest was due to accelerated apoptosis of NK cells in the BM, which prevented relatively mature BM NK cells to exit to the periphery. Finally, we identified abnormal basophil expansion as a mechanism for the Th2-biased immune responses observed in IRF-2-deficient mice. NK cell deficiency and basophil expansion was also observed in the double mutant mice mentioned above, indicating that NK cell development and basophil homeostasis were regulated in a different way than CD4+ DC development. Less
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Research Products
(14 results)
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[Journal Article] Inhibitory NK receptor Ly49Q is expressed on subsets of dendritic cells in a cellular maturation-and cytokine stimulation-dependent manner.2005
Author(s)
Toyama-Sorimachi, N., Omatsu, Y., Onoda, A., Tsujimura, Y., Iyoda, T., Maki, A., Sorimachi, H., Taki, S., Inaba, K., Karasuyama, H.
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Journal Title
J.Immunol. 174
Pages: 4621-4629
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Overexpression of human acyl CoA thioesterase upregulates peroxisome biogenesis.2004
Author(s)
Ishizuka, M., Toyama, Y., Watanabe, H., Fujiki, Y., Takeuchi, A., Yamasaki, S., Yuasa, S., Miyazaki, M., Nakajima, N., Taki, S., Saito, T.
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Journal Title
Exp.Cell.Res. 297(1)
Pages: 127-141
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Defective development of splenic and epidermal CD4^+ dendritic cells in mice deficient for interferon regulatory factor-2.2004
Author(s)
Ichikawa, E., Hida, S., Omatsu, Y., Shimoyama, S., Takahara, K., Miyagawa, S., Inaba, K., Taki, S.
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Journal Title
Proc.Natl.Acad.Sci., U.S.A. 101
Pages: 3909-3914
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Prostaglandin D2 reinforces Th2 type inflammatory responses of airway to low dose antigen through bronchial expression of macrophage-derived chemokine.2003
Author(s)
Honda, K.Arima, M.Cheng, G.Taki, S.Hirata, H.Eda, F.Fukushima, F.Yamaguchi, B.Hatano M., Tokuhisa, T., Fukuda, T.
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Journal Title
J.Exp.Med. 198
Pages: 533-543
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Predominant role of FcγRIII in the induction of accelerated nephrotoxic glomerulonephritis.2003
Author(s)
Fujii, T., Hamano, Y., Ueda, S., Akikusa, B., Yamasaki, S., Ogawa, M., Saisho, H., Verbeek, J.S., Taki, S., Saito, T.
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Journal Title
Kidney Int. 64
Pages: 1406-1416
Description
「研究成果報告書概要(欧文)」より
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