Positive selection of T cells in the thymic cortex

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H02630
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: The University of Tokushima
• Principal Investigator: TAKAHAMA Yousuke 徳島大学, 先端酵素学研究所(プロテオ), 特命教授 (20183858)
• Co-Investigator(Kenkyū-buntansha): 大東 いずみ 徳島大学, 先端酵素学研究所(プロテオ), 准教授 (00596588) ; 高田 健介 北海道大学, 大学院獣医学研究科, 准教授 (40570073)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 免疫学 / Tリンパ球 / 胸腺 / 正の選択 / レパトア

Outline of Final Research Achievements

The thymic function to produce self-protective and self-tolerant T cells is chiefly mediated by cortical thymic epithelial cells (cTECs) and medullary TECs (mTECs). Because of their limited cellularity, however, the biochemical characterization of TECs, including the proteomic profiling of cTECs and mTECs, has remained unestablished. Utilizing genetically modified mice that carry enlarged but functional thymuses, here we show a combination of proteomic and transcriptomic profiles for cTECs and mTECs, which identified signature molecules that characterize a developmental and functional contrast between cTECs and mTECs. Our results reveal a highly specific impact of the thymoproteasome on proteasome subunit composition in cTECs and provide an integrated trans-omics platform for further exploration of thymus biology.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、生命の頑強性と適応性を裏付ける獲得免疫システムを特徴づける本質の理解、とりわけ免疫学の中核的重要課題「正の選択とは何か」に関して従来の理解を大きく超えた進展をもたらし、学術の進展に寄与した。その結果、新たな免疫制御方法の可能性を示唆することによって、Ｔ細胞の分化制御に基づく新規の疾患治療法の更なる開発に向けて従来にない新技術を与える可能性を提示した。