[PDF][PDF] Commensal Lactobacillus controls immune tolerance during acute liver injury in mice

N Nakamoto, T Amiya, R Aoki, N Taniki, Y Koda… - Cell reports, 2017 - cell.com
N Nakamoto, T Amiya, R Aoki, N Taniki, Y Koda, K Miyamoto, T Teratani, T Suzuki, S Chiba…
Cell reports, 2017cell.com
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 …
Summary
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.
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