Elucidation of the mechanism underlying the regulation of adaptive immunity by endogenous double-stranded RNA

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15186
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Osaka University
• Principal Investigator: Nakahama Taisuke 大阪大学, 医学系研究科, 助教 (10636187)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: RNA編集 / 自己免疫疾患 / T細胞成熟

Outline of Final Research Achievements

Adenosine-to-inosine RNA editing catalyzed by ADAR1 is essential to prevent the recognition of endogenous dsRNA as non-self by MDA5. Although RNA editing is especially abundant in the thymus, its physiological role remains elusive. In this study, we revealed that T cell development requires coordinated regulation by ADAR1 via MDA5-dependent and -independent pathways. Furthermore, we found that T cell-specific deletion of ADAR1 in mice caused impaired negative selection to eliminate autoreactive T cells, leading to autoimmunity.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

RNA編集には内在RNAがMDA5によって非自己として認識されることを回避する機能があるが、RNA編集が胸腺において高頻度で生じるにも関わらず、その生理的意義は不明であった。本研究成果は、RNA編集が自己反応性T細胞を適切に排除し、自己免疫症状を抑える作用があることを示すものであり、自己免疫疾患の治療に向けた分子基盤情報の確立に繋がる。