Identification and elucidation of novel long non-coding RNA involved in complex formation of Satb1.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07177
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• 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): 2018-04-01 – 2021-03-31
• Keywords: 制御性T細胞 / 長鎖非翻訳RNA / Foxp3 / 自己免疫疾患

Outline of Final Research Achievements

In order to establish the molecular basis of Treg differentiation via the transcription factor Satb1, we focused on the role of Ikzf1, which a transcription factor that forms a complex with Satb1, in Treg. Then, the loss of Ikzf1 function in Treg causes abnormal activation of immune responses and the development of autoimmune disease-like lethal inflammation, suggesting that Ikzf1 plays an important role in Treg.
At the same time, we also conducted a large-scale screening using own CRISPRi system to identify novel LncRNAs involved in Treg differentiation, and succeeded in identifying many novel LncRNAs as candidates for regulators of Treg differentiation.

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の分化機構および免疫抑制機構の基礎的理解を進めた。このことから、Tregを標的とし、その量的・機能的増減による、癌、病原微生物や自己免疫疾患、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、医療応用が期待できる。