2005 Fiscal Year Final Research Report Summary
Studies on chemokines and chemokine receptors concerning migration of T-progenitor cells into the thymus anlagen
Project/Area Number |
14570288
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Immunology
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Research Institution | Meiji University of Oriental Medicine |
Principal Investigator |
AMAGAI Takashi Meiji University of Oriental Medicine, Professor, 鍼灸学部, 教授 (80094407)
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Co-Investigator(Kenkyū-buntansha) |
ITYOI Manami Meiji University of Oriental Medicine, Assistant Professor, 講師 (00257833)
TSUKAMOTO Noriyuki Meiji University of Oriental Medicine, College of Medical Technology, Assistant Professor, 講師 (80319524)
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Project Period (FY) |
2002 – 2005
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Keywords | Mouse / Thymus / T progenitor cells / Chemokine / Chemokine receptor / Cell migration / Organogenesis |
Research Abstract |
1)We report the existence of a second thymus in the neck, which develops after birth, reaching size of a small lymph node. The cervical thymus displayed a typical cortex-medulla structure, and found to be functional with regards to T cell development, and correct T cell deficiency in athymic nude mice. (Science 312, 284. 2006). 2)We showed migration of T progenitor cells into the thymus anlages occurs normally in CXCL12 mutant mice on embryonic day 11-12 comparable to that of normal littermates. However, the number of Double Negative cells in the thymus of CXCL12 mutant mice is small as compared with those of control mice. Therefore, CXCL12 do not regulate T progenitor cell migration into the thymus but proliferation of early thymocytes. (J.Immunol. 170, 4649. 2003) 3)In normal mice, endothelial precursor cells (VEcadherin+ and Flk1+) and endothelial cells (CD31+) accumulate in mesenchymal layer of the thymus anlage on Ed11-12, and migrate among the epithelial cluster of the thymus anlag
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e on Ed12-13 and form tube structure on Ed13 and thereafter. PDGFRbeta positive mesenchymal cells also migrate in the vicinity of endothelial cells among epithelial cells of the thymus anlage on Ed13. Neither endothelial precursor cells nor endothelial cells are accumulated in mesenchymal layer of the nude thymus anlage, and consequently blood vessels are not formed in the nude thymus anlage. VEGF positive epithelial cells are detected in the normal thymus anlage on Ed12-13, but not in the nude thymus anlage. It is suggested that development of thymic epithelial cells to produce VEGF, which could be controlled by the expression of Foxn1 gene, triggers vascularization of the thymus anlages. (Submitted) 4)The earliest thymic migrant cells, which express CD117 and IL7R, are identified as progenitor cells restricted to T/NK/DC lineages. (J.Immunol. 174, 2525. 2005) 5)A polycomb gene, Mel-18 regulates early T cell development in the thymus through maintenance of Hes-1 expression in developing thymocytes. (J.Immunol. 174, 2507. 2005) 6)The perivascular spaces (PVS) of the thymus in mice distribute in the corticomedullary junction surrounding large blood vessels. Our results indicate that the PVS is a transit pathway for progenitor cells to immigrate into the thymus, and for mature T cells to emigrate out from the thymus. (Submitted) Less
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Research Products
(12 results)
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[Journal Article] Evidence for a functional second thymus in mice.2006
Author(s)
Terszowski, G., Muller, S.M., Bluel C.C., Blum, C., Schirmbeck, R., Reimann, J., Pasquier, L.D., Amagai, T., Boehm, T., Rodewald, H.R.
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Journal Title
Science 312
Pages: 284-287
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Thymic anlage is colonized by progenitors restricted to T, NK and dendritic cell lineages.2005
Author(s)
Masuda, K, Itoi, M., Amagai, T., Minato, N., Katsura, Y., Kawamoto, H.
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Journal Title
J.Immunol. 174
Pages: 2525-2532
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Polycomb group gene mel-18 regulates early T progenitor expansion by maintaining the expression of Hes-1, a target of the Notch pathway.2005
Author(s)
Miyazaki, M., Kawamoto, H., Kato, Y., Itoi, M., Miyazaki, K., Masuda, K., Tashiro, S., Ishihara, H., Igarashi, K., Amagai, T., Kanno, R., Kanno, M.
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Journal Title
J.Immunol. 174
Pages: 2507-2516
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Development of thymic microenvironments in vitro is oxygen-dependent and requires permanent presence of T-cell progenitors.2003
Author(s)
Germeraad, W.T.V., Kawamoto, H., Itoi, M., Jiang, Y., Amagai, T., Katsura, Y., van Ewijk, W.
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Journal Title
J.Histochem.Cytokem. 51
Pages: 1225-1235
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A role of CXC chemokine ligand 12/stromal cell-derived factor-1/Pre-B cell growth stimulating factor and its reseptor CXCR4 in fetal and adult T cell development in vivo.2003
Author(s)
Ara, I., Itoi, M., Kawabata, K., Egawa, T., Tokoyoda, K., Sugiyama, T., Fujii, N., Amagai, T., Nagasawa, T.
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Journal Title
J Immunol 170
Pages: 4649-4655
Description
「研究成果報告書概要(欧文)」より