Examination of role of neutrophil NETs in collagen disease and application to treatment

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09913
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kurume University
• Principal Investigator: Ida Hiroaki 久留米大学, 医学部, 教授 (60363496)
• Co-Investigator(Kenkyū-buntansha): 海江田 信二郎 久留米大学, 医学部, 講師 (20330798)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: NETs / 好中球 / iPS細胞

Outline of Final Research Achievements

NETs, which are chromatin nets excreted from activated neutrophils, contain many intracellular component proteins, and not only bactericidal activity other than bacterial capture, but also thrombus formation, cancer metastasis, and the onset of collagen disease. It also plays a major role in autoantibody production. As a whole, NETs have an adverse effect on each disease except for bactericidal activity. In this study, iPS cells were established in 1 RA patient, 1 adult-onset Still's disease patient, and 5 familial Mediterranean fever patients. PMA addition and NETs were detected in normal human iPS cell-derived neutrophils. Addition of colchicine failed to inhibit NETs production.

Free Research Field

自己炎症性疾患

Academic Significance and Societal Importance of the Research Achievements

膠原病疾患、自己炎症性疾患において、NETsの構成成分の内容、NETsの量、刺激に対する反応の違いが各疾患で異なり、病変局所のみならず、全身症状にも影響を与え、病態形成に重要な役割を果たしている可能性が高い。好中球は寿命が短く解析が難しい細胞であるが、iPS細胞より誘導した好中球は比較的寿命が長いため、解析が行いやすい。コルヒチンでNETs産生が阻害できないことから、今後、NETs産生阻害薬の開発が望まれる。