Elucidation of Eosinophilic Chronic Rhinosinusitis Pathophysiology Focusing on SEMA4D-TSLP Interaction
| Project/Area Number |
17K11359
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Otorhinolaryngology
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
Maeda Yohei 大阪大学, 医学系研究科, 招聘教員 (00636483)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
端山 昌樹 大阪大学, 医学系研究科, 助教 (70756048)
|
|---|
| Project Period (FY) |
2017-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| 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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | 好酸球性副鼻腔炎 / セマフォリン / 好酸球 / アレルギー学 |
|---|
| Outline of Final Research Achievements |
We found that SEMA4D, which is expressed on eosinophils, is released from cells upon eosinophil activation and acts on endothelial cells of blood vessels and epithelial cells of the nasal cavity, loosening the bonds of blood vessels and epithelium to facilitate passage of eosinophils, which exacerbates allergic reactions and is involved in nasal polyp formation. Furthermore, SEMA4D was found to cause cytokines to be secreted from the epithelium.
In patients, blood levels of SEMA4D correlated with the severity of eosinophilic sinusitis, and patients with higher levels of SEMA4D had more severe and refractory forms of the disease. Eosinophilic sinusitis was significantly relieved in animal models.
|
| Academic Significance and Societal Importance of the Research Achievements |
好酸球上に発現しているSEMA4Dが、好酸球の活性化に伴って細胞から遊離し、血管の内皮細胞や鼻腔の上皮細胞に働きかけ、血管や上皮の結合を緩めて好酸球を通り抜けやすくすることが、アレルギー反応を悪化させ、鼻ポリープの形成に関与していることを解明したSEMA4Dを中和する抗体を用いると、動物モデルにおいて好酸球性副鼻腔炎が著明に軽快することを見出したことから、今後の診断や治療に役立つことが期待される。
|
Report
(6 results)
Research Products
(6 results)
