Clarification of the relationship between immune response and bile canaliculi destruction in hepatocytes, and its application to post-transplant liver biopsy

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07411
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Miyagawa-Hayashino Aya 京都府立医科大学, 医学(系)研究科(研究院), 講師 (90432385)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 胆管消失症候群 / 肝免疫反応 / S1P2受容体 / 毛細胆管

Outline of Final Research Achievements

VBDS is a phenomenon in which interlobular bile ducts disappear due to an immune response, leading to liver failure in advanced cases. We have previously shown that the loss of interlobular bile ducts is followed by decrease and loss of serine-threonine kinase STK17A at bile canaliculi, even before it is manifested as VBDS. In this study, we attempted to elucidate the pathogenesis of VBDS by focusing on S1P2 receptor, for which bile acids are ligands, and by studying immune cells and structural changes in bile canaliculi. S1P2 receptor expression in macrophages was increased and its inhibition decreased macrophage activity. The S1P2 receptor may interplay between macrophages and hepatocytes and induce the dilation and destruction of bile canaliculi through the RhoA/ROCK1 pathway in hepatocytes.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

免疫反応により肝内胆管が消失する現象は胆管消失症候群と総称され、造血幹細胞移植後の移植片対宿主病や肝移植後の慢性拒絶反応、薬剤性など原因は様々である。不可逆で進行すると肝不全に至るため、より早期に発見し、早期の治療介入が望まれる。本研究では、胆汁酸をリガンドとするS1P2受容体に着目し、肝内に浸潤するマクロファージと毛細胆管の構造変化からS1P2受容体を介してのVBDSの病態解明を試みた。