| Project/Area Number |
18K15183
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 49070:Immunology-related
|
|---|
| Research Institution | Shiga University of Medical Science |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2018-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | レドックスシグナル・ROS / 制御性T細胞 / 自己免疫疾患 / 活性酸素群 / 酸化ストレス / レドックス |
|---|
| Outline of Final Research Achievements |
Reactive oxygen species (ROS) have been reported to be involved in the development of autoimmunity; however, the detailed mechanism of how ROS exacerbate autoimmunity is not well defined. In this research project, we focused on redox signaling in the homeostasis of regulatory T cells (Treg) during the development of autoimmunity. Using the model of rheumatoid arthritis, Collagen-Induced Arthritis (CIA) mouse model, we demonstrated that antioxidant reagents significantly suppressed the development of arthritis. Intracellular ROS in Treg from CIA mice were highly accumulated compared to naive mice, and the number of Treg in CIA mice were significantly lower than in naive mice. Administration of antioxidants ameliorated intracellular ROS accumulation and the lowered number of Treg in CIA mice. Furthermore, PTEN, redox-sensitive phosphatase, was oxidized in Treg from CIA mice compared to naive mice.
|
| Academic Significance and Societal Importance of the Research Achievements |
免疫応答抑制の中心的役割を担うTregの生体内維持の破綻は、自己免疫疾患などの発症に大きく関与している。しかし、自己免疫疾患発症時におけるTregの維持破綻の分子機構については未だ不明な点が多い。本研究成果は、レドックスシグナルがTregの維持を制御するという新しい自己免疫疾患の発症機構に迫るものであり、新たな治療法の開発につながることが期待できる。
|
