Role of IgG4 in the pathogenesis of eosinophilic chronic rhinosinusitis

Research Project

Project/Area Number	17K16920
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Otorhinolaryngology
Research Institution	Okayama University
Principal Investigator	KOYAMA TAKAHISA 岡山大学, 大学病院, 医員 (90795270)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000) Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords	好酸球性副鼻腔炎 / IgG4 / 予後 / 鼻茸 / 好酸球性副鼻腔得 / 好酸球 / 重症度
Outline of Final Research Achievements	Background: IgG4 production is regulated by type 2 (IL-4 and IL-13) and regulatory (IL-10) cytokines involved in the pathophysiology of chronic rhinosinusitis (CRS). We sought to determine the patho- physiological characteristics of IgG4-positive cells in sinonasal tissues in CRS, especially eosinophilic CRS (ECRS). Methods: IgG4-positive cells in uncinate tissues (UT) and nasal polyps (NP) were examined by immu- nohistochemistry. Associations between the number of IgG4-positive cells and clinicopathological factors were analyzed. Results: IgG4 was mainly expressed in infiltrating plasma and plasmacytoid cells, and the number of IgG4-positive cells was significantly higher in NP, especially those from severe ECRS patients, than in UT. In CRS patients, the number of IgG4-positive cells significantly and positively correlated with blood and tissue eosinophilia, radiological severity, and serum level of total IgE.
Academic Significance and Societal Importance of the Research Achievements	好酸球性副鼻腔炎における IgG4 の病態的意義を発現および機能の面から統合的に解析するものである。特に機能解析については、独自に開発し運用している副鼻腔炎解析モデルを用いることにより、多くの新知見を見いだすことが期待できる。これは鼻副鼻腔粘膜細胞に各種菌体成分や化合物を添加することで IL-5 などのバイオマーカーを指標に好酸球性炎症への影響を評価するモデルである。好酸球性副鼻腔炎においてもマスト細胞による IgG4 産生制御機構を世界に先駆けて解明できると思われる。