Commensal Lactobacillus Controls Immune Tolerance during Acute Liver Injury in Mice

Cell Reports
Nobuhiro NakamotoTakanori Kanai

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.

Citations

Apr 24, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Viviani MendesAngelica Thomaz Vieira
Jul 3, 2019·The Journal of Clinical Investigation·Yuzo KodaTakanori Kanai
Jun 13, 2018·Frontiers in Immunology·Esther Caparrós, Rubén Francés
Jun 27, 2019·Immunotherapy·Shunfeng Hu, Xin Wang
Jul 13, 2019·Frontiers in Aging Neuroscience·Carolina OsorioAdonis Sfera
Jun 12, 2020·Nature·Toshiaki TerataniTakanori Kanai
Mar 21, 2019·Seminars in Immunopathology·Yuya HagiharaTakanori Kanai
Jun 2, 2018·BioMed Research International·Md Abul Kalam AzadJie Yin
Dec 11, 2020·Gut Microbes·André A SantosCecília M P Rodrigues
Jun 24, 2020·Seminars in Cancer Biology·Nirmala SehrawatAnil K Sharma
Nov 1, 2020·Cellular and Molecular Gastroenterology and Hepatology·Shengmin YanXiao-Ming Yin
Mar 19, 2021·Frontiers in Immunology·Mariano Prado AcostaBernd Lepenies
Jun 16, 2021·MSystems·Longxian LvYing Yu

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