Relevance of complement in Inflammatory bowel disease and potential treatment with novel complement regulators

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17440
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Takasumi Mika 福島県立医科大学, 医学部, 助教 (10836331)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: レクチン経路 / 補体 / sMAP-Ig

Outline of Final Research Achievements

In inflammatory bowel disease, lectin pathway(LP) and alternative pathway (AP) as part of the complement activation cascade were contributed to disease activity. In the past study, we generated novel complement inhibitors sMAP-FH(LP and AP regulators) and sMAP-Ig (LP regulators). Then, we evaluated the efficacy of sMAP-FH and sMAP-Ig in inflammatory bowel disease. The disease models of inflammatory bowel disease were created in wild-type mice and treated with sMAP-Ig and sMAP-FH as therapeutic agents, respectively. Although sMAP-FH did not improve the pathological condition, mice treated with sMAP-Ig showed improvement in DAI (Disease activity index) and histopathological score. Our results indicate that LP is a target for treatment of inflammatory bowel disease.

Free Research Field

消化器分野

Academic Significance and Societal Importance of the Research Achievements

炎症性腸疾患である潰瘍性大腸炎、クローン病は近年、患者数が激増しており、病態の解明、および新たな治療法の開発が必要とされている。今回、動物実験で補体レクチン経路の阻害が病態の改善に寄与することが明らかとなった。今回使用した抗補体薬はレクチン経路を特異的に阻害するものであり、抗補体薬としてもこれまでになかった作用機序である。本研究は、炎症性腸疾患の新たな病態解明、治療法の創出につながる可能性があり、学術的にも社会的にも意義のある研究であると考えている。