A mechanism to generate the stably suppressive regulatory T cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16279
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Kyoto University
• Principal Investigator: Kawakami Ryoji 京都大学, 医生物学研究所, 特定助教 (70869114)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 免疫寛容 / 制御性T細胞 / Treg / エンハンサー / CRISPR/Cas9

Outline of Final Research Achievements

The differentiation mechanism of Foxp3-positive regulatory T cells (Treg) in the thymus was explored using mouse thymus. By combining chromatin immunoprecipitation, transposase chromatin analysis and CRISPR/Cas9 system, we demonstrated a contribution of evolutinally-conserved non-coding DNA sequences (CNSs) on the X chromosome consisting of 200 and 700 nucleotides in length is indispensable for thymic Treg differentiation and establishment of immune tolerance We also identified new progenitor cells for thymic Treg differentiation and demonstrated the existence of a new differentiation pathway mediated by synergistic effects of specific cytokines. These findings may contribute to the improvement and development of control methods for autoimmune diseases, cancer and allergies.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

制御性T細胞は自己免疫疾患、がん、アレルギーの制御に中心的な役割を果たすヘルパーT細胞サブセットである。これら疾患の多くは難治性ないし指定難病であり、免疫寛容誘導の生理学的メカニズムに基づく疾患病態の理解と治療法開発は急務である。今回新たに制御性T細胞分化メカニズムに寄与するDNA領域を明らかとし、未知のTreg前駆細胞集団をセルソータを用いて単離する技術を開発したことは、制御性T細胞分化の分子メカニズム研究を大いに進展させ、それを標的とした薬剤や治療法の開発につながるものと考える。