An innate immune response to bacterial components is speculated to be involved in the pathogenesis of
primary biliary cirrhosis (PBC). Recently, CD4-positive T helper type 17 (Th17) cells, characterized by the secretion of
interleukin (IL)-17, have been implicated in the pathogenesis of
autoimmune diseases. Human Th17 cells are generated from Th0 cells by
IL-6 and
IL-1 beta and maintained by
IL-23. In this study, the role of
IL-17 in PBC and its association with biliary innate immunity were examined. Using cultured human biliary epithelial cells (BECs), the expression of Th17-related
cytokines and
chemokines and changes therein on treatment with
pathogen-associated molecular patterns (
PAMPs) and
IL-17 were examined. Immunohistochemistry for
IL-17 and Th17-related
cytokines was performed using tissue samples of human liver. Consequently, the expression of
IL-6,
IL-1 beta,
IL-23p19 and IL-23/IL-12p40 mRNAs, and their up-regulation by
PAMPs, were found in BECs. Moreover, BECs possessed IL-17-receptors and stimulation with
IL-17 induced production of
IL-6,
IL-1 beta,
IL-23p19 and
chemokines. Several IL-17-positive cells had infiltrated damaged bile ducts and the expression of
IL-6 and
IL-1 beta was enhanced in the bile ducts of PBC patients. In conclusion, IL-17-positive cells are associated with the chronic
inflammation of bile ducts in PBC which is associated causally with the biliary innate immune responses to
PAMPs.