title: Aetiopathogenesis of autoimmune hepatitis.
abstract: Interface hepatitis, histological hallmark of autoimmune hepatitis (AIH), is a dense portal mononuclear cell infiltrate invading the parenchyma, consisting of CD4 and CD8 T-lymphocytes, monocytes/macrophages and plasma cells. What triggers AIH is unknown, but there is evidence that failure of immune homeostasis plays a permissive role allowing liver autoantigen-specific cells to attack hepatocytes. Damage is likely to be orchestrated by CD4 T-lymphocytes recognizing an autoantigenic liver peptide. For autoimmunity to arise, the peptide, embraced by an HLA class II molecule, must be presented to naïve CD4 T-helper (T(H)0) cells by professional antigen-presenting cells. Once activated, T(H)0 cells can differentiate into T(H)1 cells, which are pivotal to macrophage activation, enhance HLA class I expression, rendering liver cells vulnerable to CD8 T-cell attack, and induce HLA class II expression on hepatocytes; or into T(H)2 cells producing IL-4, IL-10 and IL-13, cytokines favouring autoantibody production by B-lymphocytes. Autoantigen recognition is tightly controlled by regulatory mechanisms, such as those exerted by CD4+CD25+ regulatory T-cells (T-regs). Numerical and functional T-reg impairment characterizes AIH, particularly during active disease. Advances in the study of autoreactive T-cells stem mostly from AIH type 2, where the main autoantigen, CYP2D6, is known enabling characterization of antigen-specific immune responses. Monocyte involvement in the autoimmune liver attack has been recently reported.
authors.affiliation: Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, Denmark Hill, London SE5 9RS, UK.
authors.forename: Maria Serena
authors.initials: MS
authors.lastname: Longhi
authors.forename: Yun
authors.initials: Y
authors.lastname: Ma
authors.forename: Giorgina
authors.initials: G
authors.lastname: Mieli-Vergani
authors.forename: Diego
authors.initials: D
authors.lastname: Vergani
mesh_terms: D000818:Animals; D017209:Apoptosis; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019389:Cytochrome P-450 CYP2D6 / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D019693:Hepatitis, Autoimmune / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D018716:Molecular Mimicry; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D016207:Cytokines; D019389:Cytochrome P-450 CYP2D6