Cellular interactions in self-directed immune-mediated liver diseases.

The lymphocyte population must traverse a complex path throughout their journey to the liver. The signals which these cells must detect, including cytokines, chemokines and other soluble factors, steer their course towards further crosstalk with other hepatic immune cells, hepatocytes and biliary epithelial cells. A series of specific chemokine receptors and adhesion molecules drive not only the recruitment, migration, and retention of these cells within the liver, but also their localisation. Perturbation of these interactions and failure of self-recognition drive the development of several autoimmune liver diseases. We also describe check point-induced liver injury. Immune cell internalisation into hepatocytes (emperipolesis) in autoimmune hepatitis and into biliary epithelial cells (intra-epithelial lymphocyte) in primary biliary cholangitis are typical features in autoimmune liver diseases. Finally, we describe emerging immune-based therapies, including regulatory T cell, anti-cytokine and anti-chemokine therapies, cytokine supplementation (e.g. interleukin-2), as well as co-inhibitory molecule manipulation, including T-cell engagers, and discuss their potential application in the treatment of autoimmune liver diseases.