Aetiopathogenesis of autoimmune hepatitis

TY - JOUR

T1 - Aetiopathogenesis of autoimmune hepatitis

AU - Longhi, Maria Serena

AU - Ma, Yun

AU - Mieli-Vergani, Giorgina

AU - Vergani, Diego

PY - 2010/2

Y1 - 2010/2

N2 - 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 if molecule, must be presented to naive 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. (C) 2009 Elsevier Ltd. All rights reserved.

AB - 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 if molecule, must be presented to naive 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. (C) 2009 Elsevier Ltd. All rights reserved.

U2 - 10.1016/j.jaut.2009.08.010

DO - 10.1016/j.jaut.2009.08.010

M3 - Literature review

VL - 34

SP - 7

EP - 14

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

IS - 1

ER -