Molecular basis for T cell repertoire formation in thymic microenvironment

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05202
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: The University of Tokyo
• Principal Investigator: Nitta Takeshi 東京大学, 大学院医学系研究科(医学部), 准教授 (30373343)
• Research Collaborator: SAWA Shinichiro ; MURO Ryunosuke ; OKAMURA Tadashi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 免疫学 / 細胞・組織 / 胸腺 / T細胞 / 自己免疫

Outline of Final Research Achievements

T cells develop in the thymus, where various stromal cells including thymic epithelial cells regulate development and repertoire selection of immature T cells. Here, using a series of genetically modified mice, we studied the developmental mechanism and function of thymic epithelial cells. Our results showed that membrane-bound RANKL expressed in immature T cells is required for the development of medullary thymic epithelial cells. We also found that a PSMB11 gene polymorphism that is frequently found in the Japanese population impairs the function of cortical thymic epithelial cells and alters T cell repertoire in mice. In addition, we identified stromal factors and signaling proteins that determine the fate of distinct subsets of gamma/delta T cells in the thymus.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

T細胞は私たちの免疫系の司令塔であり、その抗原認識能力がつくられるしくみを理解することは、感染防御やがん免疫治療の観点から重要な課題である。本研究では、T細胞の抗原認識を決定づける胸腺微小環境のはたらきについて研究し、胸腺上皮細胞の生成のしくみと機能の一端を明らかにした。特に、日本人に高頻度にみられる遺伝子変異がT細胞の抗原認識と自己免疫疾患リスクに影響を与えることを見出したことは、大きな成果といえる。