Commensal Lactobacillus Controls Immune Tolerance during Acute Liver Injury in Mice.

Abstract

Gut-derived microbial antigens trigger the innate immune system during acute liver injury. During recovery, regulatory immunity plays a role in suppressing inflammation; however, the precise mechanism underlying this process remains obscure. Here, we find that recruitment of immune-regulatory classical dendritic cells (cDCs) is crucial for liver tolerance in concanavalin A-induced acute liver injury. Acute liver injury resulted in enrichment of commensal Lactobacillus in the gut. Notably, Lactobacillus activated IL-22 production by gut innate lymphoid cells and raised systemic IL-22 levels. Gut-derived IL-22 enhanced mucosal barrier function and promoted the recruitment of regulatory cDCs to the liver. These cDCs produced IL-10 and TGF-β through TLR9 activation, preventing further liver inflammation. Collectively, our results indicate that beneficial gut microbes influence tolerogenic immune responses in the liver. Therefore, modulation of the gut microbiota might be a potential option to regulate liver tolerance.

• Authors: Nobuhiro Nakamoto, Takeru Amiya, Ryo Aoki, Nobuhito Taniki, Yuzo Koda, Kentaro Miyamoto, Toshiaki Teratani, Takahiro Suzuki, Sayako Chiba, Po-Sung Chu, Atsushi Hayashi, Akihiro Yamaguchi, Shunsuke Shiba, Rei Miyake, Tadashi Katayama, Wataru Suda, Yohei Mikami, Nobuhiko Kamada, Hirotoshi Ebinuma, Hidetsugu Saito, Masahira Hattori, Takanori Kanai
• Journal: Cell reports (Cell Rep) Vol. 21 Issue 5 Pg. 1215-1226 (Oct 31 2017) ISSN: 2211-1247 [Electronic] United States
• PMID: 29091761 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Histocompatibility Antigens Class II
• Interleukins
• Toll-Like Receptor 9
• Transforming Growth Factor beta
• Interleukin-10
• Interferon-gamma
• Alanine Transaminase
• interleukin-22

Topics

• Alanine Transaminase (blood)
• Animals
• Chemical and Drug Induced Liver Injury (immunology, pathology)
• Dendritic Cells (cytology, metabolism)
• Gastrointestinal Microbiome
• Histocompatibility Antigens Class II (metabolism)
• Immune Tolerance
• Immunity, Innate
• Interferon-gamma (metabolism)
• Interleukin-10 (metabolism)
• Interleukins (metabolism)
• Intestinal Mucosa (metabolism)
• Intestines (immunology, microbiology)
• Lactobacillus (immunology, physiology)
• Liver (immunology, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• T-Lymphocytes, Regulatory (cytology, immunology, metabolism)
• Toll-Like Receptor 9 (metabolism)
• Transforming Growth Factor beta (metabolism)