It is widely known that a variety of immune cells in the liver contribute to the pathogenesis of liver diseases. Recently, roles of chemokines/chemokines receptors axes regarding the migration of immune competent cells to the inflamed liver have been reported as possible therapeutic targets. We here showed that CCR9+ CD11b+ macrophages play an important role during the course of Concanavalin A-induced murine acute liver injury as well as human acute hepatitis via the production of inflammatory cytokines and the Th1 induction. Further analysis using liver-shielded radiation and bone marrow (BM) transplantation model mice revealed that these CCR9+ CD11b+ macrophages are originated from BM-derived monocytes, but not liver resident macrophages (Kupffer cells). Furthermore, these CD11b+ inflammatory macrophages in contact with hepatic stellate cells contribute to the pathogenesis of murine experimental liver fibrosis via CCR9/CCL25 axis. Collectively, these results with further verification in human samples clarify the pathogenic role of CCR9/CCL25 axis as therapeutic target of a variety of liver diseases.
ASJC Scopus subject areas
- Immunology and Allergy