2001 Fiscal Year Final Research Report Summary
New therapeutic approach for ollergic disease based on genome informatics
| Project/Area Number |
12670441
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | Research Institute Biological Sciences, Tokyo Universjty of Science |
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Principal Investigator |
MASATO Kubo Research Institute Biological Sciences, Tokyo Universjty of Science,Associate,professor, 生命科学研究所, 助教授 (40277281)
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| Project Period (FY) |
2000 – 2001
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| Keywords | genome / T cell differentiation / Th1 / Th2 / IL-4 |
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| Research Abstract |
The differentiation of naive, uncommitted Th cell precursors into Thi or Th2 cells is cell-cycle dependent process that is initiated by antigen and cytokine stimulation. Both T cell receptor (TCR) cross-linking and Interleukin (IL)-4 is known to be required for onset of Th2 commitment. However, how these two signals synergistically regulate Th2 differentiation poorly understand. We established the transgenic mice expressing human lL-4 receptor (hlL-4R Tg) to distinguish IL-4-dependent signal from TCR signal during induction of helper T cell differentiation. The addition of hlL-4 at initial ICR stimulation completely substituted the function of endogenous lL-4 required for Th2 generation. Timedependent kinetics analysis revealed that the presence of IL-4 within 36 hr after TCR activation that a large number of T cells remained at first cell cycle, was a critical for the onset of Th2 commitment and chromatin remodeling on IL-4 gene locus. In contrast, the addition of lL-4 after proceeding cell division did not result in efficient Th2 differentiation. In TCR activated T cells from hlL-4R Tg, GATA-3 expression was depend on the addition of hlL-4 even at the time points when no Th2 cells was generated. Ectopic expression of GATA-3 showed that timing and expression level was critical for determination of lineage commitment towards Th2 cells. These results indicate that a direction of I cell commitment is almost determined at first cell division, and IL-4 mediated GATA-3 expression at this stage may control efficient Th2 differentiation.
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Research Products
(17 results)
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[Publications] Tokoyoda, K., Takemoto, Y., Nakayama, T., Arai, T., and Kubo, M: "Synergism between the calmodulinbinding domain and the auto-inhibitory domain on calcineurin is essential for the induction of their phosphatase activity."J. Biol. Chem,. 275,16. 11728-11734 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Kimura, M., Yamashita, M., Kubo, M., Iwashima, M., Shimizu, C., Chiba, J., Taniguchi, M., Katsumata, M., and Nakayama, T.: Int. Immunol. 12. 817-824 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Masuda, A., Masuguchi, T., Yamaki, K., Hayakawa, T., Kubo, M., LaRochelle, W.J., and Yoshikai, Y.: "Interleukin-15 induces rapid tyrosine-phosphorylation of STAT6 and the expression of lnterukin-4 in mouse mast cells."J. Biol. Chem. 275,38. 29331-29337 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Suzuki, A., Hanada, T., Mitsuyama, K., Yoshida, T., Kamizono, S., Hoshino, T., Kubo, M., Yamashita, A., Okabe, M., Toyonaga, A., Sata, M., Yoshimura, A., :: J. Exp. Med. 193. 471-482 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Harada, Y, Tanabe, E., Weiss, B.D., Kubo, M., June, C.H., and Abe, R: "Novel role of PI3-K in CD28-mediated costimulation."J. Biol. Chem. 276. 9003-9008 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Hanada, T., Yoshida, T., Kinjyo, I., Minoguchi, S., Yasukawa, H., Kato, S., Mimata, H., Nomura, Y, Seki, Y, Kubo, M., and Yoshimura, A: "A mutant form of JAB/SOCS1 augments the form of JAB/SOCS1 augments the cytokine-induced JAK/STAT pathway by accelerating degradation of wildtype JAB/CIS family proteins through the SOCS-box."J. Biol. Chem. 276. 40746-40754 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Yagi, R., Suzuki, W., Seki, N., Inoue, T., Kohyama, M., Arai, T., and Kubo, M.: "The IL-4 Production Capability of Different Strains of Naive CD4+ T cells controls the Direction of the Helper T cell response."Int. lmunol.. 14,1. 1-11 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Yagi, R., Nagai, H., ligo, Y, Akimoto, T., Aral, T., and Kubo, M.:: "Development of the atopic dermatitis (AD)-like skin lesions in signal transducers and activators of transcription (STAT) 6 deficient NC/Nga mice."J. Immunol.. 168. 2020-2027 (2002)
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「研究成果報告書概要(欧文)」より
