Fundamental research for the development of new immune response regulation methods targeting Foxp3 binding factor Ikzf1

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02748
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Osaka University
• Principal Investigator: Ichiyama Kenji 大阪大学, 免疫学フロンティア研究センター, 特任准教授(常勤) (60777960)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Ikzf1 / Foxp3 / 制御性T細胞 / 転写因子複合体 / 自己免疫疾患

Outline of Final Research Achievements

To develop the new immune disease therapies targeting regulatory T cells (Treg), we examined the role of the interaction between the transcription factors Foxp3 and Ikzf1 in Treg function. The disruption of the interaction between Foxp3 and Ikzf1 in Treg resulted in induction of epigenomic changes around Treg-related genes, which in turn disrupts Treg-specific gene expression patterns and Treg functional stability, leading to excessive immune responses and ultimately to the development of lethal autoimmune disease-like inflammation. Furthermore, Ikzf1 also played an important role in maintaining functional stability of human Treg.

Free Research Field

分子免疫学

Academic Significance and Societal Importance of the Research Achievements

正常個体中に存在する制御性T細胞(Treg)は、異常・過剰な免疫反応の抑制に特化したT細胞群であり、免疫自己寛容、免疫恒常性の維持に中心的な役割を果たしている。そしてその異常は、自己免疫病、アレルギー疾患、炎症性腸炎などの直接的原因となることが知られている。本研究成果は、Tregの機能安定性機構の基礎的理解を発展させた。今後、これら知見を基にヒトTregを標的とし、その量的・機能的増減による、がんや自己免疫疾患、移植臓器拒絶反応に対する新しい免疫応答制御法の開発、医療応用に繋がることが期待できる。