Immune-mediated liver injury.
Diseases with different pathogeneses share common pathways of immune-mediated injury. Autoreactive T cells destroy hepatocytes or cholangiocytes in autoimmune disease and virus-specific T cells destroy infected hepatocytes in viral hepatitis. In these conditions, antigen-specific mechanisms can be implicated but immune-mediated injury is central to diseases where there is a less-defined role for specific antigens. In all these diseases, "bystander cells" activated by the local microenvironment rather than a specific antigen are major players and amplify effector responses by recruiting natural killer and natural killer T cells, macrophages, neutrophils, eosinophils, and even platelets. Immune-mediated liver injury is driven by repeated cycles of inflammation and damage sustained by continuing recruitment, retention, and survival of effector leukocytes within the inflamed liver. These processes depend on complex interactions involving epithelial cells, stromal cells, and leukocytes shaped by the local cytokine microenvironment. Understanding these interactions will elucidate the pathogenesis of liver disease and suggest new therapies.
Eksteen
Bertus
B
Liver Research Group, MRC Centre for Immune Regulation, Institute of Biomedical Research, University of Birmingham Medical School, Birmingham, United Kingdom.
Afford
Simon C
SC
Wigmore
Stephen J
SJ
Holt
Andrew P
AP
Adams
David H
DH
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006505:Hepatitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000293:injuries / Q000378:metabolism; D008107:Liver Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008954:Models, Biological
D016207:Cytokines