Publication Date:
2017-01-22
Description:
The incidence and prevalence of inflammatory liver diseases has increased over the last years but therapeutic options are limited. Pregnancy induces a state of immune tolerance, which can result in spontaneous improvement of clinical symptoms of certain autoimmune diseases including autoimmune hepatitis (AIH). We investigated the immune suppressive mechanisms of the human pregnancy hormone chorionic gonadotropin (hCG) in the liver. HCG signaling activates SIRT1, which deacetylates FOXO3a, leading to repression of pro-apoptotic gene expression. As immunosuppressive consequence due to the absence of Caspase-3 activity hepatocellular IL-16 is no longer processed and released. Thus serum levels of IL-16, a key chemotactic factor for CD4+ lymphocytes, were reduced and migration to injured hepatocytes prevented. Further, elevated IL-16 levels are found in the sera from patients with autoimmune hepatitis, HBV, HCV and NASH. Conclusion : Here we report that hCG regulates the SIRT1/FOXO3a axis in hepatocytes resulting in immune suppression by attenuating Caspase-3 dependent IL-16 processing and release, which concomitantly prevents auto-aggressive T cell infiltration to the liver. Considering the low toxicity profile of hCG in humans, interrupting the inflammatory cycle by hCG opens new perspectives for therapeutic intervention of inflammatory liver diseases. This article is protected by copyright. All rights reserved.
Print ISSN:
0270-9139
Electronic ISSN:
1527-3350
Topics:
Medicine
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