Fig. 8.

Overall schema of the initiation of PBC. Exposure to environmental xenobiotics alters gut microbiota composition and induces intestinal inflammation. Gut microbiota membrane components and TNF-α induces apoptosis of BECs, which leads to autoantigen release. Injured BECs express more adhesion molecules ICAM-1 and chemoattractants CCL2, CXCL9, and CXCL10 to recruit immune cells. Among infiltrated immune cells in the portal area, CD8 T cells are responsible for further biliary destruction by secreting more IFN-γ and cytotoxic molecules perforin and granzyme B.