Generation of humanized mice to analyze human MHC-restricted T cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06469
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: Kyoto University
• Principal Investigator: Kometani Kohei 京都大学, iPS細胞研究所, 特定拠点助教 (50437258)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 胸腺上皮細胞

Outline of Final Research Achievements

To induce human Thymic Epithelial cell (TEC) from human iPS cells, I generated iPS cell lines which induce the expression of transcription factor essential for TEC development in a doxycycline-dependent manner. The iPS cells were induced into definitive endoderm which is the original germ layer of TECs. Then, doxycycline was added to the culture medium and the culture was continued. After the culture, gene expression of the cells was analyzed by qPCR. The result suggests that the TEC-progenitor like cells are induced by this method.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

ヒト免疫細胞のin vivoでの解析には、免疫細胞をヒト由来細胞と置き換えた「免疫ヒト化マウス」の利用が有用である。しかしながら、既存の免疫ヒト化マウスでは胸腺上皮細胞がレシピエントであるマウス由来であり、分化するヒトT細胞がマウスMHCと結合して分化するため、ヒトT細胞としての機能が完全ではなかった。一方、今回の研究で得られたヒト胸腺上皮前駆細胞様細胞を免疫ヒト化マウスに移植することで、ヒト胸腺環境を備え機能的なヒトT細胞が発生する改良型免疫ヒト化マウスを作製し、ヒトT細胞の生体内での機能を解析できる可能性が提示された。