| Project/Area Number |
16H06387
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (S)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Immunology
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
SHIBUYA AKIRA 筑波大学, 生存ダイナミクス研究センター, 教授 (80216027)
|
|---|
| Project Period (FY) |
2016-05-31 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥185,380,000 (Direct Cost: ¥142,600,000、Indirect Cost: ¥42,780,000)
Fiscal Year 2020: ¥30,680,000 (Direct Cost: ¥23,600,000、Indirect Cost: ¥7,080,000)
Fiscal Year 2019: ¥33,410,000 (Direct Cost: ¥25,700,000、Indirect Cost: ¥7,710,000)
Fiscal Year 2018: ¥33,020,000 (Direct Cost: ¥25,400,000、Indirect Cost: ¥7,620,000)
Fiscal Year 2017: ¥32,110,000 (Direct Cost: ¥24,700,000、Indirect Cost: ¥7,410,000)
Fiscal Year 2016: ¥56,160,000 (Direct Cost: ¥43,200,000、Indirect Cost: ¥12,960,000)
|
|---|
| Keywords | 自然免疫 / 抑制性免疫受容体 / アレルギー / 炎症 / 抑制性受容体 / CD300a / Allergin-1 / Clec10a / 免疫受容体 |
|---|
| Outline of Final Research Achievements |
The immune response requires a mechanism to control the excessive immune response. The purpose of this study was to understand the negative regulatory mechanism of the innate immune response by dendritic cells, macrophages, neutrophils, mast cells, and to elucidate the significance of inhibitory immune receptors in the innate immune response. In this study, we identified the ligands of CD300a, Allergin-1, and Clec10a. In addition, binding of these inhibitory receptors to their respective ligands suppressed FceRI;RI, TLR2, and TLR4 signals via tyrosine phosphatase SHP-1, and inhibited activation of mast cells, dendritic cells, macrophages. As a result, they control allergic and inflammatory pathologies in organs such as skin, airway, and intestinal tract. Therefore, these inhibitory receptors can be target molecules for these diseases.
|
| Academic Significance and Societal Importance of the Research Achievements |
自然免疫反応は獲得免疫応答とは異なり抗原感作を必要とせず、DAMPsや炎症性メディエーターなど生体内部で生じる分子をパターン認識受容体で認識し速やかに作動しうるが、これは常に自己傷害の危険性をはらんでいる。それに対して、抑制性免疫受容体は、その周囲に常に存在する内在性リガンドと速やかに結合することによって、自己寛容を担っていることが明らかとなった。研究により、それらのリガンドの共通の特徴が明らかにされたことにより、自然免疫応答の負の制御機構の一端が明瞭になった。さらに、これらの性質を理解することによって、抑制性免疫受容体を標的としたアレルギー、炎症性疾患に対する分子標的療法の可能性が拓けた。
|
| Assessment Rating |
Verification Result (Rating)
A
|
Assessment Rating |
Result (Rating)
A: Progress in the research is steadily towards the initial goal. Expected research results are expected.
|
