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| Status |
Public on Dec 10, 2019 |
| Title |
Intestinal IL-17R signaling controls liver inflammation by constraining microbiome-induced TLR9 signaling and IL-18 production |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
IL-17 and IL-17R signaling in the intestinal epithelium regulate the intestinal microbiome. Given the reported links between intestinal dysbiosis, bacterial translocation, and liver disease, we hypothesized that intestinal IL-17R signaling plays a critical role in mitigating hepatic inflammation. To test this, we studied intestinal epithelial-specific IL-17RA deficient mice in a model of concanavalin A hepatitis. Absence of enteric IL-17RA signaling exacerbated hepatitis and hepatocyte cell death. These mice exhibited commensal dysbiosis, increased intestinal and liver Il18, and increased liver translocation of bacterial products, specifically CpG DNA. Mechanistically, CpG DNA induced hepatic IL-18, increasing IFNγ and FasL in hepatic T-cells to drive inflammation. 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 seen in other extra-intestinal pathologies.
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| Overall design |
Liver mRNA profiles of 6-week old Il17ra fl/fl mice and Il17ra fl/fl x villin cre+ mice at the naïve state and 90 minutes post concanavalin a injection (n=2 mice/genotype/timepoint)
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| |
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| Contributor(s) |
Kolls JK, Hand TW, Chen K |
| Citation(s) |
31747600 |
| Submission date |
Mar 14, 2019 |
| Last update date |
Dec 10, 2019 |
| Contact name |
Jay K Kolls |
| E-mail(s) |
jkolls1@tulane.edu
|
| Phone |
504-988-0456
|
| Organization name |
Tulane University School of Medicine
|
| Department |
Center for Translational Research in Infection and Inflammation
|
| Street address |
333 S. Liberty St, JBJ 375
|
| City |
New Orleans |
| State/province |
LA |
| ZIP/Postal code |
70112 |
| Country |
USA |
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| Platforms (1) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA527218 |
| SRA |
SRP188556 |
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