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 Saito & 2 others Masahira Hattori, Takanori Kanai

    Research output: Contribution to journalArticle

    13 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

    Fingerprint

    Immune Tolerance
    Lactobacillus
    Liver
    Wounds and Injuries
    Dendritic Cells
    Lymphocytes
    Inflammation
    Immune system
    Concanavalin A
    Interleukin-10
    Immune System
    Immunity
    Chemical activation
    Modulation
    interleukin-22
    Antigens
    Recovery

    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)

    Cite this

    Nakamoto, N., Amiya, T., Aoki, R., Taniki, N., Koda, Y., Miyamoto, K., ... 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

    Commensal Lactobacillus Controls Immune Tolerance during Acute Liver Injury in Mice. / Nakamoto, Nobuhiro; Amiya, Takeru; Aoki, Ryo; Taniki, Nobuhito; Koda, Yuzo; Miyamoto, Kentaro; Teratani, Toshiaki; Suzuki, Takahiro; Chiba, Sayako; Chu, Po Sung; Hayashi, Atsushi; Yamaguchi, Akihiro; Shiba, Shunsuke; Miyake, Rei; Katayama, Tadashi; Suda, Wataru; Mikami, Yohei; Kamada, Nobuhiko; Ebinuma, Hirotoshi; Saito, Hidetsugu; Hattori, Masahira; Kanai, Takanori.

    In: Cell Reports, Vol. 21, No. 5, 31.10.2017, p. 1215-1226.

    Research output: Contribution to journalArticle

    Nakamoto, N, Amiya, T, Aoki, R, Taniki, N, Koda, Y, Miyamoto, K, Teratani, T, Suzuki, T, Chiba, S, Chu, PS, Hayashi, A, Yamaguchi, A, Shiba, S, Miyake, R, Katayama, T, Suda, W, Mikami, Y, Kamada, N, Ebinuma, H, Saito, H, Hattori, M & Kanai, T 2017, 'Commensal Lactobacillus Controls Immune Tolerance during Acute Liver Injury in Mice', Cell Reports, vol. 21, no. 5, pp. 1215-1226. https://doi.org/10.1016/j.celrep.2017.10.022
    Nakamoto N, Amiya T, Aoki R, Taniki N, Koda Y, Miyamoto K et al. Commensal Lactobacillus Controls Immune Tolerance during Acute Liver Injury in Mice. Cell Reports. 2017 Oct 31;21(5):1215-1226. https://doi.org/10.1016/j.celrep.2017.10.022
    Nakamoto, Nobuhiro ; Amiya, Takeru ; Aoki, Ryo ; Taniki, Nobuhito ; Koda, Yuzo ; Miyamoto, Kentaro ; Teratani, Toshiaki ; Suzuki, Takahiro ; Chiba, Sayako ; Chu, Po Sung ; Hayashi, Atsushi ; Yamaguchi, Akihiro ; Shiba, Shunsuke ; Miyake, Rei ; Katayama, Tadashi ; Suda, Wataru ; Mikami, Yohei ; Kamada, Nobuhiko ; Ebinuma, Hirotoshi ; Saito, Hidetsugu ; Hattori, Masahira ; Kanai, Takanori. / Commensal Lactobacillus Controls Immune Tolerance during Acute Liver Injury in Mice. In: Cell Reports. 2017 ; Vol. 21, No. 5. pp. 1215-1226.
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