| Project/Area Number |
17K09992
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Collagenous pathology/Allergology
|
|---|
| Research Institution | University of Occupational and Environmental Health, Japan |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | 関節リウマチ / サイトカイン / 滑膜 / DNAメチル化 / エピゲノム / 滑膜細胞 / エピジェネティクス / 炎症性サイトカイン / TET3 / 糖鎖修飾 / 内科 / 発現制御 |
|---|
| Outline of Final Research Achievements |
In rheumatoid arthritis (RA), which is a representative autoimmune disease, it is assumed that epigenetic alterations occur in the synovium under the inflammatory environment, resulting in the acquisition of a trait that is more prone to joint destruction and refractory to treatment. In a series of studies, we found that the DNA demethylase TET3 was induced by inflammatory cytokines including TNFα and altered the expression of many genes. As an epigenetic gate-keeper in the pathogenesis of RA, TET3 may play a key role in prolonging inflammation.
|
| Academic Significance and Societal Importance of the Research Achievements |
近年、関節リウマチ（RA）においては、生物学的製剤やJAK阻害剤などの分子標的薬の登場により、寛解を目指した治療が可能となったが、分子標的療法でもその３割から４割は治療抵抗性を示し、治療経過とともに難治化する。今回の研究成果は、TET3を標的としたRA滑膜におけるエピゲノム異常の是正が、RA治療のブレークスルーとなりうる可能性を示唆した。
|
