title: Role of inflammatory macrophages and CCR9/CCL25 chemokine axis in the pathogenesis of liver injury as a therapeutic target.
abstract: 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.
authors: Department of Internal Medicine, Keio University School of Medicine.
authors: Nobuhiro
authors: N
authors: Nakamoto
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000502:physiology; D019742:Chemokines, CC / Q000502:physiology*; D055166:Hepatic Stellate Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008107:Liver Diseases / Q000188:drug therapy* / Q000209:etiology*; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D058990:Molecular Targeted Therapy; D054388:Receptors, CCR / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C119309:CC chemokine receptor 9; C108074:CCL25 protein, human; D039481:CD11b Antigen; D019742:Chemokines, CC; D018836:Inflammation Mediators; D054388:Receptors, CCR; D014157:Transcription Factors; C118437:negative elongation factor