Elucidation of the mechanisms by which an inhibitory receptor regulates the development of autoimmune subepidermal bullous diseases

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08782
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Juntendo University
• Principal Investigator: Izawa Kumi 順天堂大学, 大学院医学研究科, 特任准教授 (80708313)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 抑制型受容体 / 好中球 / 免疫複合体

Outline of Final Research Achievements

Bullous pemphigoid, which is caused by autoantibody to type XVII collagen (COL17), and epidermolysis bullosa acquisita, which is caused by autoantibody to type VII collagen (COL7), are autoimmune subepidermal bullous diseases. We administered antibody to COL17 or COL7 to mice, that induced bullous pemphigoid or epidermolysis bullosa acquisita, respectively, in mice. As compared to wild type mice, neutrophil-deficient mice exhibited the decline in clinical scores and the reduction of inflammatory cell infiltration in skin in these models, indicating that neutrophil activation is responsible for the development of these diseases. On the other hand, CD300f deficiency did not significantly the severity of these diseases in mice. These results suggested that CD300f failed to regulate the activation of neutrophils by immune complexes in these models.

Free Research Field

アレルギー・炎症

Academic Significance and Societal Importance of the Research Achievements

マウスモデルの解析により、表皮下水疱症の病態形成に好中球の活性化が重要であることが確認された。一方、表皮下水疱症モデルにおいて、抑制型受容体CD300fは免疫複合体による好中球の活性化を抑制しないこと、CD300fは表皮下水疱症の治療標的として不適であることが判明した。本研究成果は、免疫複合体による好中球の活性化を強く抑制する治療法を開発するための基礎となるので、その学術的意義や社会的意義が存在すると考えられる。