Roles of complement system in development of hypersensitivity pneumonitis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23840
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Okamoto Tsukasa 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (60724200)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 補体活性化 / 過敏性肺炎 / 間質性肺炎 / マウスモデル

Outline of Final Research Achievements

We made hypersensitivity pneumonitis (HP) mouse model using pigeon dropping extracts (PDE). The number of lymphocytes in bronchoalveolar lavage fluid (BALF) of PDE mice increased in 1 week, which was an early phase, and decreased graduately after that. On the other hands, the number of neutrophils and macrophases increased during 1 to 3 weeks. The granulomas were identified around vessels and bronchioles in the mouse lungs.
C5a levels in BALF and plasma of PDE mice was higher compared to saline control. C5a levels increased most at 24 hours after the last dose. These data suggested that complement activation was occurred during the acute phase of pathogenesis in HP mouse model.

Free Research Field

間質性肺炎

Academic Significance and Societal Importance of the Research Achievements

吸入抗原が原因とされる過敏性肺炎には免疫複合体と補体活性化が密接にかかわっていることが予想される。本研究の成果によって、過敏性肺炎において補体活性化が病態に重要であり、かつ補体経路のどの経路の活性化が大切か明らかにすることができれば、現在多くの補体阻害剤がある中で臨床試験につなげることが可能となり、治療への応用が期待できる。さらに、急性期の補体活性化を抑制することができれば、慢性化への移行（線維性過敏性肺炎への進行）を抑制できる可能性がある。