| Theme |
PSC and PBC -- Recent Progress in Diagnosis and Treatment |
| Title |
Recent Topics Related to PBC Pathogenesis |
| Author |
Kazumichi Abe |
Department of Gastroenterology and Rheumatology, Fukushima Medical University |
| Author |
Atsushi Takahashi |
Department of Gastroenterology and Rheumatology, Fukushima Medical University |
| Author |
Hiromasa Ohira |
Department of Gastroenterology and Rheumatology, Fukushima Medical University |
| [ Summary ] |
Primary biliary cirrhosis (PBC) is characterized by chronic non-suppurative destructive cholangitis, a condition that leads to destruction of interlobular bile ducts. An autoimmune mechanism, along with cellular senescence, linked to genetic and environmental factors, are believed to contribute to PBC pathogenesis. Recently, genome-wide association studies (GWAS) have identified TNFSF1 and POU2AF1 as novel disease-susceptibility genes related to the development of PBC in the Japanese population. As for immunological factors, the expression of Toll-like receptors (TLR) has been observed in biliary epithelial cells. Reports suggest a mechanism wherein the destruction of biliary epithelial cells by activated NK cells occurs due to stimulation by TLR3 and TLR4 ligands and a shift to Th1, leading to chemokine production and infiltration of infammatory cells. Moreover, the presence of autoreactive T-cells and B-cells, and how these cells are associated with the emergence of AMA and destruction of biliary epithelial cells, have also been reported. These recent findings are gradually unraveling the mechanisms underlying PBC pathogenesis. |