The study for the protective response by innate immune system and functional specialization of Kupffer cells in the pathogenesis of NASH

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461010
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kochi University
• Principal Investigator: ONO Masafumi 高知大学, 教育研究部医療学系臨床医学部門, 准教授 (70304681)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ＮＡＳＨ / Kupffer細胞 / CD68+Kupffer細胞 / CD11b+Kupffer細胞 / 腸内細菌

Outline of Final Research Achievements

Although impairment of Kupffer cells are important for the pathogenesis of nonalcoholic steatohepatitis (NASH), the precise mechanisms of the impairment have not been well clarified yet. In this study, we have clarified that the CD11b+Kupffer cells increased and CD68+Kupffer cells decreased in the liver of NASH. In addition, inflammation and fibrosis were improved without attenuation of hepatic steatosis, when CD11b+Kupffer cells were decreased by exposing of 1Gy irradiation. In contrast, depletion of the resident subset, CD68+Kupffer cells, by clodronate liposome (c-lipo) treatment exacerbated disease progression. It was clarified that recruited CD11b+ CD68+ Kupffer cells may play an essential role in steatohepatitis and fibrosis in the pathogenesis of NASH. We concluded that recruitment and activation of bone marrow derived macrophages, CD11b+Kupffer cells, may have the important key factor to develop steatohepatitis from simple steatosis.

Free Research Field

NASH