| Project/Area Number |
17K09995
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Collagenous pathology/Allergology
|
|---|
| Research Institution | Chiba University |
|---|
Principal Investigator |
Suto Akira 千葉大学, 大学院医学研究院, 准教授 (50447306)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
鈴木 浩太郎 千葉大学, 大学院医学研究院, 准教授 (90554634)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | IL-21 / γδT細胞 / 自己免疫性筋炎 / GM-CSF |
|---|
| Outline of Final Research Achievements |
IL-21 is involved in the development of various autoimmune diseases; however, the role of IL-21 in autoimmune inflammatory myopathies remains unknown. Here, we found that serum levels of IL-21 were significantly elevated in patients with inflammatory myopathies. Upon the induction of experimental autoimmune myositis (EAM), muscle weakness was less obvious in IL-21-deficient (IL-21-/-) mice as compared to that in wild-type mice. GM-CSF from γδT cells was significantly reduced in EAM-induced IL-21-/- mice. The severity of EAM was attenuated by GM-CSF neutralization or γδT cell-deficiency. Majority of muscle-infiltrating γδT cells expressed Vγ4+Vδ4+ TCR and exhibited CX3CR1high phenotype. The induction of Cx3cl1, a ligand for CX3CR1, in the muscles by EAM was reduced in IL-21-/- mice. Taken together, these results suggest that IL-21 facilitates autoimmune myositis through the accumulation of GM-CSF-producing Vγ4+Vδ4+ cells in the muscles possibly via CX3CR1/CX3CL1 pathways.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究の特色は、炎症性筋疾患発症におけるIL-21の役割に着目していることである。本研究者は以前よりIL-21の産生機構、及び自己免疫疾患におけるIL-21の役割に関する研究に従事し、多くの実績を残している。本申請研究は、炎症性筋疾患モデルにIL-21が関与していることをIL-21欠損マウスを用いた研究で明らかにし、さらに炎症性筋疾患患者で血清中IL-21濃度が高いことを見出しており、炎症性筋疾患の病態にIL-21が関与していることが強く示唆される。本申請研究は、炎症性筋疾患の治療法の開発に繋がる可能性も高く、その臨床的意義は大きいと考える。
|
