Development of prophylactic strategies for acute and chronic radiation-induced gastrointestinal syndrome by targeting the innate immune system

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K19148
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Osaka University (2018-2019); Chiba University (2016-2017)
• Principal Investigator: Takemura Naoki 大阪大学, 薬学研究科, 講師 (50648699)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 放射線性消化管症候群 / 自然免疫 / 放射線誘導性腸線維症 / 好酸球 / 放射線誘導性口腔内粘膜炎 / TLR3

Outline of Final Research Achievements

Gastrointestinal syndrome is the most troublesome side effect of radiation therapy that occurs during the acute and chronic phases if the gastrointestinal tract is exposed to high doses of radiation for cancer treatment. In this project, we investigated the role of innate immunity in the pathogenesis of gastrointestinal syndrome. Consequentially, we elucidated the disease mechanisms of radiation-induced intestinal fibrosis (RIF), in which eosinophils play a critical role in activation of intestinal myofibroblasts to promote fibrogenesis, and proposed eosinophil-depleting agents as an effective prophylactic measure for the management of RIF. In addition, we also found that epithelial damage via the activation of Toll-like receptor 3 (TLR3) post-irradiation is a critical event for ulcer formation and subsequent leukocyte infiltration in radiation-induced oral mucositis (RIOM), and suggested TLR3 inhibitors as a potential preventive measure against RIOM.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

放射線性消化管症候群のうち、腸線維症と口腔内粘膜炎はいずれも病態成立過程が十分に明らかとなっていないため、対症療法以外に手立てがなく、癌患者の生活の質を大きく低下させる問題となっている。本研究により、それぞれの疾患の病態成立過程において好酸球やTLR3を中心とした自然免疫機構が重要な役割を果たすことが明らかとなったことで、当該機構を標的とした新たな予防・治療戦略の開発が進むと期待される。また、同様の対処法は、耐容線量の増加や放射線治療期間の延長によって放射線療法のがん治療効果を向上させるという目的のためにも応用されることが期待される。