Role of extracellular traps in gastrointestinal inflammation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15276
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Yasuda Hiroyuki 京都薬科大学, 薬学部, 助教 (40780284)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 細胞外トラップ / 消化管炎症 / IBD / PADI2 / PADI4

Outline of Final Research Achievements

The purpose of this study was to clarify the involvement of NETs and METs in the pathology of gastrointestinal inflammation including IBD, focusing on PADI2 and PADI4, and the induction mechanism of NETs and METs. NETs and METs were induced in TNBS-induced colitis or DSS-induced colitis, and it was revealed that NETs mediated by PADI4 are involved in the pathogenesis of TNBS-induced colitis. In contrast, the pathology of DSS-induced colitis was aggravated in PADI2 and PADI4KO mice. These results suggest that PADI2 and PADI4KO are involved in the pathogenesis of IBD in an extracellular trap-dependent or -independent manner.

Free Research Field

薬理系薬学

Academic Significance and Societal Importance of the Research Achievements

以前より、様々な疾患において細胞外トラップの関与が示唆されてきたが、IBDなどの消化管炎症に細胞外トラップが関与するか検討した研究は少なく、NETsとMETsの誘導比較という観点から検討した研究はない。本研究では、消化管炎症において細胞外トラップが免疫応答の一端に関与することを明らかにした。このとき、細胞外トラップ依存的な病態形成だけでなく、PADI2とPADI4を介した細胞外トラップ非依存的な経路によってIBDの病態が進行する可能性があるという結果も得られ、より詳細な病態形成機構の解明に向けた重要な情報を提供できたと考える。