Elucidation and novel therapies development for granuloma formation in chronic granulomatous disease

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10104
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Shinshu University
• Principal Investigator: Shigemura Tomonari 信州大学, 学術研究院医学系(医学部附属病院), 講師 (70623916)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 慢性肉芽腫症 / 活性酸素 / 肉芽腫 / 腸炎

Outline of Final Research Achievements

Chronic granulomatosis disease (CGD) is accompanied by granulomas and enteritis as well as susceptibility to infections due to reduction of reactive oxygen species (ROS) from phagocytes. We hypothesized that phagocytes without ROS production would cause abnormal immunity and compared the differences in inflammation-related expression in phagocytes caused by ROS production. However, no clear difference was found in this study. In the study of rare disorder caused impaired maturation of neutrophil, which is a type of phagocytes, clones with impaired maturation did not affect normal neutrophil differentiation. On the other hand, the research of particular kind of enteritis disease revealed the involvement of acquired immune abnormality in enteritis associated with granulomas. These findings suggest that abnormalities in acquired immunity caused by ROS may be involved in the pathology of CGD.

Free Research Field

免疫

Academic Significance and Societal Importance of the Research Achievements

慢性肉芽腫症(CGD)は食細胞の機能異常のため易感染性を示すことから、CGDでみられる肉芽腫や肉芽腫を伴う腸炎の病態にも食細胞が強く関わっているとされてきた。今回の研究からCGDの肉芽腫形成に、食細胞以外の獲得免疫の異常が関与することが示唆された。そのことは肉芽腫を基本病態とするクローン病、サルコイドーシス、肉芽腫性血管炎、また単一遺伝子疾患である若年性サルコイドーシスなどに対しても重要な知見であり、それらの肉芽腫疾患に対しても大きな福音と成り得る。