RESUMO
Background: Interleukin-34 (IL-34) is an important immunomodulatory factor that plays a crucial role in a variety of autoimmune diseases. Aims: To investigate the expression of IL-34 in primary biliary cholangitis (PBC) and its influence on intrahepatic inflammation and bile duct damage. Methods: Liver tissues were obtained from 26 PBC patients and 10 hepatic hemangioma patients without PBC. Expression and localization of IL-34 were detected by immunohistochemistry. In animal experiment, Poly I:C intraperitoneal injection was used to construct PBC model in wild-type and IL-34-knockout C57BL/6 mice (WT-PBC group and IL-34KO-PBC group). Subsequently, the intrahepatic inflammation and bile duct damage were evaluated pathologically, and the expressions of IL-34 and associated cytokines in liver tissues were detected by real-time PCR and Western blotting. Results: Expression of IL-34 in liver tissues of PBC patients and PBC model mice was significantly higher as compared with those of the controls (all P<0.05). No morphological changes in hepatic pathological evaluation were observed in IL-34KO mice receiving intraperitoneal saline injection. In IL-34KO-PBC mice, the portal area inflammation and biliary epithelial cell damage were more severe than those in WT-PBC mice (all P<0.05). Expressions of proinflammatory cytokine interleukin-1β (IL-1β) and monocyte chemotactic protein-1 (MCP-1) in liver tissues of IL-34KO-PBC mice were significantly increased than those of WT-PBC mice, whereas expressions of antiinflammatory cytokine IL-10 and CD163, the surface marker of M2 macrophages, were significantly reduced (all P<0.05). Conclusions: IL-34 expression is increased in liver tissues of PBC patients and animals. It might reduce the portal area inflammation and bile duct damage via modulating cytokines expression and driving macrophages polarization to the M2 phenotype. IL-34 might act as a self-rescue factor which negatively regulates hepatic immune microenvironment and prevents disease progression.
