The liver has several unique immunological properties that affect T cell activation and immune regulation. Recent studies have uncovered opportunities for the treatment of genetic disease by directing expression of the functional therapeutic protein to hepatocytes. In a new study in this issue of the JCI, Lüth and colleagues demonstrate that hepatic expression of a brain protein is protective against neuroinflammatory disease in a mouse model of human MS (see the related article beginning on page 3403). Suppression of autoimmunity was dependent on transgene expression in the liver and was mediated by induction of antigen-specific CD4+CD25+Foxp3+ Tregs. These findings suggest that the introduction of antigens to the liver may have potential as a preventative or therapeutic intervention for autoimmune disease.