Commensal Lactobacillus Controls Immune Tolerance during Acute Liver Injury in Mice

Publication date: 31 October 2017
Source:Cell Reports, Volume 21, Issue 5
Author(s): 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
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.

Graphical abstract

Teaser

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.


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