Identification of medullary thymic epithelial stem cells
| Project/Area Number |
24590580
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Kyoto University |
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Principal Investigator |
Hamazaki Yoko 京都大学, 医学(系)研究科(研究院), 准教授 (10362477)
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 胸腺 / 中枢性自己寛容 / 胸腺上皮細胞 / 幹細胞 / 胸腺退縮 / 自己免疫疾患 / Aire / 自己寛容 / 胸腺上皮幹細胞 |
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| Outline of Final Research Achievements |
Medullary thymic epithelial cells (mTECs) are crucial for central T cell self-tolerance. We demonstrate that implantation of embryonic TECs expressing claudin-3 and claudin-4 (Cld3,4) in a medulla-defective thymic microenvironment restores medulla formation and suppresses multiorgan autoimmunity throughout life. A minor SSEA-1(+) fraction within the embryonic Cld3,4(hi) TECs contained self-renewable clonogenic TECs, capable of preferentially generating mature mTECs in vivo. Adult SSEA-1(+)Cld3,4(hi) TECs retained mTEC reconstitution potential, although the activity decreased. The clonogenicity of TECs also declined rapidly after birth in wild-type mice, whereas it persisted in Rag2 knock out adult mice with defective thymopoiesis. The results suggest that unipotent mTEC-restricted stem cells that develop in the embryo have the capacity to functionally reconstitute the thymic medulla long-term, thus ensuring lifelong central T cell self-tolerance.
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Report
(5 results)
Research Products
(32 results)
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[Journal Article] In vivo imaging reveals PKA regulation of ERK activity during neutrophil recruitment to inflamed intestines.2014
Author(s)
Mizuno, R., Kamioka, Y., Kabashima, K., Imajo, M., Sumiyama, K., Nakasho, E., Ito, T., Hamazaki, Y., Okuchi, Y., Sakai, Y., Kiyokawa, E., and Matsuda, M.
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Journal Title
J Exp Med
Volume: 211
Issue: 6
Pages: 1123-36
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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