Role of epithelial glycosylation in the development of allergic airway inflammation
| Project/Area Number |
17K09645
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Respiratory organ internal medicine
|
|---|
| Research Institution | Chiba University |
|---|
Principal Investigator |
Hirose Koichi 千葉大学, 大学院医学研究院, 特任教授 (90400887)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
玉地 智宏 千葉大学, 大学院医学研究院, 特任講師 (20456015)
岩田 有史 千葉大学, 大学院医学研究院, 助教 (90436353)
|
|---|
| 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: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | アレルギー性気道炎症 / 気道上皮細胞 / フコシル化 / Fut2 / 補体 / 単球由来樹状細胞 / 気道上皮フコシル化 / 補体経路 / IL-13 / STAT6 / 気管支喘息 / 糖鎖修飾 / フコース転移酵素 / Th2細胞 / 起動上皮細胞 |
|---|
| Outline of Final Research Achievements |
One of the pathognomonic features of asthma is epithelial hyperproduction of mucus which is composed of a series of glycoproteins; however, it remains unclear how glycosylation is induced in asthmatic lung epithelial cells and how glycan residues play a role in the pathogenesis of asthma. Using lectin micro-array, we found that upon allergen inhalation, lung epithelial cells were heavily alpha(1,2)fucosylated by fucosyltransferase 2 (Fut2). Importantly, Fut2-deficient mice (Fut2-/- mice) exhibited significantly attenuated eosinophilic inflammation, airway hyperresponsiveness and significantly reduced levels of C3a and impaired accumulation of C3a receptor-expressing monocyte-derived dendritic cells (Mo-DCs) in the lung of HDM-induced allergic asthma model mice. Taken together, these results suggest that Fut2 induces epithelial fucosylation and exacerbates airway inflammation in asthma in part via C3a production and Mo-DC accumulation in the lung.
|
| Academic Significance and Societal Importance of the Research Achievements |
気管支喘息の臨床的特徴の一つに気道における粘液過剰産生が含まれること、またこの粘液中には多くの糖タンパク質が存在することは古くから知られていたが、糖鎖修飾がアレルギー性炎症にいかなる働きを持つかは不明であった。本研究ではアレルギー性気道炎症により誘導される糖鎖修飾を網羅的に解析し、惹起された糖鎖修飾が如何にして炎症を増悪させるかを明らかにした。
本研究により気管支喘息の新たな病態が明らかにされた。これらの知見を応用することによって、既存治療では十分な治療効果が得られていない喘息患者に対する新たな治療機軸の確立が可能となる可能性がある。
|
Report
(4 results)
Research Products
(27 results)
-
[Journal Article] Fucosyltransferase 2 induces lung epithelial fucosylation and exacerbates house dust mite-induced airway inflammation.2019
Author(s)
Saku A, Hirose K, Ito T, Iwata A, Sato T, Kaji H, Tamachi T, Suto A, Goto Y, Domino SE, Narimatsu H, Kiyono H, Nakajima H
-
Journal Title
J Allergy Clin Immunol.
Volume: 144(3)
Issue: 3
Pages: 698-709
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
-
[Journal Article] Sox12 promotes T reg differentiation in the periphery during colitis.2018
Author(s)
anaka S, Suto A, Iwamoto T, Kageyama T, Tamachi T, Takatori H, Suzuki K, Hirose K, Ohara O, Lefebvre V, Nakajima H.
-
Journal Title
J Exp Med.
Volume: 215
Issue: 10
Pages: 2509-2519
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Eosinophilic vasculitis affecting multiple middle-sized arteries in a patient with Kimura's disease: A case report and literature review2018
Author(s)
Furuya H, Ikeda K, Suzuki J, Suzuki K, Nakamura K, Furuta S, Tamachi T, Suzuki K, Hirose K, Nakajima H.
-
Journal Title
Allergology International
Volume: 67
Issue: Supplement.1
Pages: S45-S47
DOI
NAID
ISSN
1323-8930, 1440-1592
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
