Commensal Lactobacillus Controls Immune Tolerance during Acute Liver Injury in Mice

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 SaitoMasahira Hattori, Takanori Kanai

Research output: Contribution to journalArticle

21 Citations (Scopus)

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. Nakamoto et.al. find that Lactobacillus accumulates in the gut and activates IL-22 production by innate lymphoid cells during acute liver injury. Gut-derived IL-22 contributes to liver tolerance via induction of regulatory DCs.

Original languageEnglish
Pages (from-to)1215-1226
Number of pages12
JournalCell Reports
Volume21
Issue number5
DOIs
Publication statusPublished - 2017 Oct 31

Keywords

  • acute liver injury
  • dendritic cell
  • dysbiosis
  • immune tolerance
  • innate lymphoid cell
  • interleukin-10
  • interleukin-22
  • microbiota

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Nakamoto, N., Amiya, T., Aoki, R., Taniki, N., Koda, Y., Miyamoto, K., Teratani, T., Suzuki, T., Chiba, S., Chu, P. S., Hayashi, A., Yamaguchi, A., Shiba, S., Miyake, R., Katayama, T., Suda, W., Mikami, Y., Kamada, N., Ebinuma, H., ... Kanai, T. (2017). Commensal Lactobacillus Controls Immune Tolerance during Acute Liver Injury in Mice. Cell Reports, 21(5), 1215-1226. https://doi.org/10.1016/j.celrep.2017.10.022