Regulatory T cells (Tregs) have a profound ability to control immune responses. A majority of Tregs are derived from the thymus; yet a substantial Treg fraction is derived from the periphery. The liver seems to be an important source of peripherally derived Tregs. Indeed, the liver's well-known ability to induce immune tolerance is at least partly based on hepatic Treg generation. With recently developed tools to deliver
antigens to tolerance-inducing liver cells, it is now possible to harness liver-derived Tregs for specific control of unwanted immune responses. Indeed, the selective delivery of
autoantigens to liver sinusoidal endothelial cells could induce
autoantigen-specific Tregs in vivo, providing effective treatment of
autoimmune disease. Owing to the fundamental role Tregs play in controlling immune responses, an impairment of Tregs seems to be a plausible explanation for the development of
autoimmune diseases, for example, in the liver. However, the actual role of Treg impairment in autoimmune
liver diseases, such as
autoimmune hepatitis (AIH), remains controversial. Major obstacles for clarifying the role of Tregs in autoimmune
liver diseases are related to the difficulty to identify human Tregs unambiguously and to the difficulty to identify those Tregs and effector T cells that specifically recognize disease-driving
autoantigens. However, even if AIH turned out to be a disease that is not driven by Treg impairment, Treg-based
therapies for autoimmune
liver diseases might still be effective, provided the Tregs for
therapeutic use recognize the relevant
antigens.