2002 Fiscal Year Final Research Report Summary
Molecular signals that regulate the development and movements of developing T lymphocytes
| Project/Area Number |
12470077
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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 | The University of Tokushima |
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Principal Investigator |
TAKAHAMA Yousuke The University of Tokushima, Institute for Genome Research, Professor, ゲノム機能研究センター, 教授 (20183858)
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| Project Period (FY) |
2000 – 2002
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| Keywords | T lymphocyte / T cell-receptor / thymus / CCL19 / apoptosis / Nurr77 / Stat3 / Chemokine |
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| Research Abstract |
Signals that regulate the development and selection of T lymphocytes in the thymus have been studied. We have found that T-cell receptor-mediated signals activated Akt, which phosphorylated Nur77 and thereby antagonized Nur77-mediated apoptosis of T cells, suggesting that T-cell receptor-mediated positive and negative selection can be controlled by Akt-mediated phophorylation of Nur77. We have also found that the mice in which Stat3 gene in thymic epithelial cells has been specifically disrupted by the keratin 5 promoter developed severe thymic hypoplasia and exhibited a high susceptibility of the thymus to suboptimal doses of dexamethasone or gamma-irradiation, indicating that Stat3 in thymic epithelial cells plays an essential role in maintaining thymic architecture and thymocyte survival. Moreover, we have found that CCR7-ligand chemokine CCL19 attracted mature T cells out of the fetal thymus organ culture, and that neonatal appearance of circulating T cells was defective in CCR7-deficient mice, indicating that CCR7-dependent pathway of thymic emigration represents a major pathway of neonatal T cell export.
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[Publications] Hayashi, K., Natsume, W., Watanabe, T., Abe, N., lwai, N., Okada, H., Ito, Y., Asano, M., Iwakura, Y., Habu, S., Takahama, Y. and Satake, M.: "Diminution of the AML1 transcription factor function causes differential effects on the fates of CD4 and CD8 single positive T cells."J. Immunol.. 165. 6816-6824 (2000)
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[Publications] Masuyama, N., Oishi, K., Mori, Y., Ueno, T., Takahama, Y. and Gotoh, Y.: "Akt inhibits the orphan nuclear receptor Nur77 and T cell apoptosis."J. Biol. Chem.. 276. 32799-32805 (2001)
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[Publications] Sano, S., Takahama, Y., Sugawara, T., Kosaka, H., Itami, S., Miyazaki, J., van Ewijk, W. and Takeda, J.: "Stat3 in thymic epithelial cells is essential for postnatal maintenance of thymic architecture and thymocyte survival."Immunity. 15. 261-273 (2001)
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[Publications] Yoh, K., Sugawara, T., Motohashi, H., Takahama, Y., Koyama, A., Yamamoto, M. and Takahashi, S.: "Transgenic overexpression of MafK suppresses T cell proliferation and function in vivo."Genes to Cells. 6. 1055-1066 (2001)
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[Publications] Ueno, T., Hara, K., Swope Willis, M. Malin, M. Hoepken, U., Gray, D.H.D.Matsushima, K., Lipp, M., Springer, T.A.Boyd, R.L., Yoshie, O. and Takahama, Y.: "Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus."Immunity. 16. 205-218 (2002)
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[Publications] Akamatsu, Y., Monroe, R., Dudley, D.D., Elkin, S.K., Gartner, F., Talukder, S.R., Takahama, Y., Alt, F.W., Bassing, C.H. and Oettinger, M.A.: "Deletion of the RAG2 C-terminus leads to impaired lymphoid development in mice."Proc. Natl. Acad. Sci. USA.. 100. 1209-1214 (2003)
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