Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Intestinal barrier regulates immune responses in the liver via IL-10–producing macrophages
Nobuhito Taniki, … , Hirotoshi Ebinuma, Takanori Kanai
Nobuhito Taniki, … , Hirotoshi Ebinuma, Takanori Kanai
Published June 21, 2018
Citation Information: JCI Insight. 2018;3(12):e91980. https://doi.org/10.1172/jci.insight.91980.
View: Text | PDF
Research Article Hepatology Immunology

Intestinal barrier regulates immune responses in the liver via IL-10–producing macrophages

  • Text
  • PDF
Abstract

The gut-liver axis is of clinical importance as a potential therapeutic target in a wide range of liver diseases; however, the mechanisms underlying interactions between microbial products and immune responses in the liver remain unknown. In this study, we demonstrated that IL-10–producing macrophages contribute to immune tolerance in the inflamed liver under intestinal barrier disruption in a murine tandem model of dextran sulfate sodium (DSS) colitis and concanavalin A (Con A) hepatitis. Intestinal barrier disruption protected mice from subsequent liver injury, and the severity of colitis directly affected susceptibility to such injury. The protective effect of DSS–Con A was canceled in gut-sterilized mice, suggesting that gut microbiota play a substantial role in this process. Altered gut microbiota and their metabolites, along with a disrupted intestinal barrier, directly gave rise to immunological permissiveness in the inflamed liver. We identified 1-methylnicotinamide (1-MNA) as a candidate metabolite capable of suppressing liver injury with the potential to induce IL-10–producing macrophages. Consistently, expression of nicotinamide N-methyltransferase, which converts nicotinamide to 1-MNA, was upregulated in the liver of DSS–Con A mice, and this effect was abrogated by gut sterilization. Collectively, our results provide a mechanistic insight into the regulation of immunological balance in the liver via the gut-liver axis.

Authors

Nobuhito Taniki, Nobuhiro Nakamoto, Po-Sung Chu, Yohei Mikami, Takeru Amiya, Toshiaki Teratani, Takahiro Suzuki, Tomoya Tsukimi, Shinji Fukuda, Akihiro Yamaguchi, Shunsuke Shiba, Rei Miyake, Tadashi Katayama, Hirotoshi Ebinuma, Takanori Kanai

×

Figure 5

Continuous exposure to gut-derived products directly affects the susceptibility to subsequent liver injury.

Options: View larger image (or click on image) Download as PowerPoint
Continuous exposure to gut-derived products directly affects the suscept...
(A) Antibiotic cocktails or single antibiotics were orally administrated 6 times over a 2-week period, followed by DSS–Con A treatment. (B) Body weight and DAI on days 0–7 of mice in each group (n = 6/group). Data represent the mean ± SEM. **P < 0.01 according to 1-way ANOVA with Tukey’s multiple-comparison correction. (C) Serum ALT level in mice from each experimental group (n = 4–6/group). Data represent the mean ± SEM. *P < 0.05 according to a 2-tailed Student’s t test.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts