To clarify the autoreactive T cells in Graves' Disease using single cell analysis

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16417
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Hashimoto Yoshitaka 京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (70806140)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: バセドウ病 / T細胞 / TCR配列 / 単一細胞解析

Outline of Final Research Achievements

The purpose of this study was to identify T cells that respond to TSH receptor-derived antigen peptides in Graves' disease and to determine their TCR sequence expression genes and cell surface markers. Single cell sequencing was performed on PBMCs from patients with Graves' disease. We found the significant changes were observed in T cell. Moreover, according to the TCR repertoire analysis, we found that TRAV29/DV5/ TRAJ42 in TRA and TRBV10-3/ TRBJ2-1 pairs in TRB were frequently observed in all cells, Memory CD4 T-cells, Memory CD8 T-cells and T-reg.

Free Research Field

内分泌・代謝

Academic Significance and Societal Importance of the Research Achievements

バセドウ病の病態の中核は甲状腺刺激ホルモン(TSH)受容体を刺激する自己抗体の産生であるが、これに関与する自己反応性T細胞の同定が不十分であるため、TSH受容体由来抗原ペプチドに反応するT細胞を同定し、そのTCR配列発現遺伝子及び細胞表面マーカーを明らかにすることを目的として検討をした結果、関連するTCR配列発現遺伝子及び細胞表面マーカーを明らかにすることができた。今後は今回の結果をもとにバセドウ病の早期発見や新たな創薬開発に繋げていくことが可能になると考える。