Identification of medullary thymic epithelial stem cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 24590580
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Kyoto University
• Principal Investigator: Hamazaki Yoko 京都大学, 医学(系)研究科(研究院), 准教授 (10362477)
• Project Period (FY): 2012-04-01 – 2016-03-31
• 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

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.

Free Research Field

免疫学