Application of a new biomarker LRG to real-world clinical practice of inflammatory bowel disease

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08371
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Iwate Medical University (2021); Kochi University (2019-2020)
• Principal Investigator: FUJIMOTO MINORU 岩手医科大学, 医学部, 准教授 (00379190)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: バイオマーカー / サイトカイン

Outline of Final Research Achievements

LRG, one of our research seeds, has become a laboratory test to evaluate disease activity of inflammatory bowel disease (IBD). In this study, we investigated the regulatory mechanism of LRG expression in IBD. By using cell lines derived from hepatocytes and intestinal LRG-producing cells (intestinal epithelial cells, monocytes, neutrophils), we found that STAT3 and NFκB, the major transcription factors of inflammatory cytokines, are the key inducers of LRG production in many cell types including hepatocytes. On the other hand, in neutrophils, LRG expression was induced cytokine-independently during their differentiation and maturation process. Gene expression analysis using a next-generation sequencer reveled that immune signals represented by NFκB are enhanced in human IBD tissues, which likely promotes LRG production in gastrointestinal lesions.

Free Research Field

臨床免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究は、サイトカイン下流の転写因子の中で炎症形成に特に重要なSTAT3とNFκBが、肝細胞や病変部位の細胞でLRG発現を直接制御すること、それとは別の機序が好中球のLRG産生を促すことを明らかにした。一方、既存マーカーCRPは、IL-6が肝細胞にてSTAT3を活性化するという単一的機序で発現が誘導される。以上から、CRPよりもさらに幅広い病態でLRGが上昇すること、自然免疫系シグナルの亢進がみられるIBD粘膜の病態は、CRPよりもLRGによく反映されること、が強く示唆され、IBD診療におけるLRG測定の優位性とその理論的根拠が示された。