Modulation of the longevity proteins FOXO3a and SIRT1 by chorionic gonadotropin prevents hepatocellular injury during acute liver inflammation

During pregnancy, the clinical improvement of autoimmune hepatitis is frequently observed. The understanding of this phenomenon is incomplete both from the side of the immune system and the liver. Using a murine model of autoimmune hepatitis and adult human hepatocytes in primary culture, we could show that the pregnancy hormone, human chorionic gonadotropin (hCG) regulates the longevity proteins FOXO3a and SIRT1, which permit hepatocytes to tolerate destructive T cell attack and protects mice from T cell-dependent liver injury. hCG-signaling induced the nuclear exclusion of wild type, but not phosphorylation-re…