Elucidation of the mechanism underlying the regulation of adaptive immunity by endogenous double-stranded RNA
| 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 |
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
|---|
| Keywords | RNA編集 / 自己免疫疾患 / T細胞成熟 / Adar1 / 獲得免疫 |
|---|
| 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.
|
| 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。
|
Report
(4 results)
Research Products
(11 results)
-
[Journal Article] RNA editing at a limited number of sites is sufficient to prevent MDA5 activation in the mouse brain.2021
Author(s)
Jung In Kim, Taisuke Nakahama, Ryuichiro Yamasaki, Pedro Henrique Costa Cruz, Tuangtong Vongpipatana, Maal Inoue, Nao Kanou, Yanfang Xing, Hiroyuki Todo, Toshiharu Shibuya, Yuki Kato, Yukio Kawahara.
-
Journal Title
PLoS Genet
Volume: 未定(In Press)
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
