Abstract：
:Interleukin (IL)-17 signaling to the intestinal epithelium regulates the intestinal microbiome. Given the reported links between intestinal dysbiosis, bacterial translocation, and liver disease, we hypothesize that intestinal IL-17R signaling plays a critical role in mitigating hepatic inflammation. To test this, we study intestinal epithelium-specific IL-17RA-deficient mice in an immune-driven hepatitis model. At the naive state, these mice exhibit microbiome dysbiosis and increased translocation of bacterial products (CpG DNA), which drives liver IL-18 production. Upon disease induction, absence of enteric IL-17RA signaling exacerbates hepatitis and hepatocyte cell death. IL-18 is necessary for disease exacerbation and is associated with increased activated hepatic lymphocytes based on Ifng and Fasl expression. Thus, intestinal IL-17R regulates translocation of TLR9 ligands and constrains susceptibility to hepatitis. These data connect enteric Th17 signaling and the microbiome in hepatitis, with broader implications on the effects of impaired intestinal immunity and subsequent release of microbial products observed in other extra-intestinal pathologies.
journal_name
Cell Repjournal_title
Cell reportsauthors
Castillo-Dela Cruz P,Wanek AG,Kumar P,An X,Elsegeiny W,Horne W,Fitch A,Burr AHP,Gopalakrishna KP,Chen K,Methé BA,Canna SW,Hand TW,Kolls JKdoi
10.1016/j.celrep.2019.10.042subject
Has Abstractpub_date
2019-11-19 00:00:00pages
2270-2283.e7issue
8issn
2211-1247pii
S2211-1247(19)31356-7journal_volume
29pub_type
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