Mechanisms of autoimmune hepatitis

Abstract

Purpose of review: Autoimmune hepatitis (AIH) is a chronic disease characterized by a lymphocyte infiltrate in the liver. For decades, nonspecific immunosuppression has been used to limit chronic liver inflammation. The high risk of relapse, the treatments side effects, and the significant number of refractory patients are the main clinical issues that require efforts to understand AIH immune mechanisms.

Recent findings: The balance between regulatory CD4 T cells, known to control autoimmunity, and effector CD4 T cells, that recognize liver self-antigens and mediate the liver inflammation, appears central in AIH immune mechanisms. Recent advances in the identification of pathogenic auto-reactive CD4 T cells, and of new mechanisms of immune regulatory defects in AIH patients, give new insights into the pathophysiology of this disease.

Summary: In this review, we propose an overview of the central role of CD4 T cells (both regulatory and pathogenic) in mechanisms of AIH, with a focus on recent advances regarding defective regulatory mechanisms and immune profile of auto-reactive CD4 T cells. These findings may have implication for the orientation of new therapeutic strategies to treat AIH, such as regulatory T-cell infusion or targeting B cells and cytokines released by pathogenic CD4 T cells.