Investigation of T cell senescence-related pathogenesis of chronic inflammatory diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09658
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Kamekura Ryuta 札幌医科大学, 医学部, 講師 (70404697)
• Co-Investigator(Kenkyū-buntansha): 一宮 慎吾 札幌医科大学, 医学部, 教授 (30305221) ; 高野 賢一 札幌医科大学, 医学部, 教授 (70404689)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 老化関連 T 細胞 / Tph2 細胞 / 免疫老化

Outline of Final Research Achievements

We analyzed T peripheral helper (Tph) cells and extrafollicular B cells (age-associated B cells, ABCs) in peripheral blood from patients with IgG4-related disease (IgG4-RD). The percentages of ICOS+ Tph cells, Ki-67+ Tph cells and ABCs were increased in IgG4-RD patients compared with the percentages of those cells in healthy controls. The percentages of Tph2 cells were also increased in blood from patients with IgG4-RD. The percentage of Tph2 cells was positively correlated with clinical parameters including serum IgG4 and number of involved organs. In addition, the percentage of blood Tph2 cells was positively correlated with the percentage of blood ABCs, suggesting that Tph2 cells interact with ABCs in affected organs of IgG4-RD. Moreover, the percentage of IgG4+ cells in ABCs was increased in blood from patients with IgG4-RD compared with the percentage of IgG4+ cells in non-ABCs. The results suggest that ABCs are a main source of serum IgG4 in IgG4-RD.

Free Research Field

免疫・アレルギー

Academic Significance and Societal Importance of the Research Achievements

免疫老化の観点から慢性炎症性疾患の病態を捉え、加齢に伴い増加する PD-1 陽性メモリー CD4 T 細胞である末梢ヘルパー T (Tph) 細胞の機能を明らかにすることで、IgG4 関連疾患などの高齢者に多い慢性炎症性疾患の病態解明と新規治療法の開発、高齢者の免疫能の低下を補いワクチンの効果を高めることで免疫老化を予防する新たなモダリティの開発に繋がる。