Molecular mechanisms of portal vein tolerance.
The liver has been considered as a tolerogenic organ in the sense that favors the induction of peripheral tolerance. The administration of antigens (Ags) via the portal vein causes tolerance, which is termed portal vein tolerance and can explain the occurrence of tolerogenic responses in the liver. Here we discuss the fundamental mechanisms accounting for portal vein tolerance. Antigen-presenting cells (APCs) in the liver, especially dendritic cells and sinusoidal endothelial cells, have limited the ability to produce pro-inflammatory cytokines upon stimulation with endotoxin, an effect that could be due to the continuous exposure to bacterial Ags derived from intestinal microflora. Ag presentation by liver APCs results in T cell tolerance through clonal deletion and selection of regulatory T cells. Thus, APCs with immunosuppressive functions are associated with the achievement of portal vein tolerance via the induction of clonal deletion and generation of regulatory T cells.
Watanabe
Tomohiro
T
Department of Gastroenterology and Hepatology, and Department of Clinical Bio-Regulatory Science, Kyoto University Graduate School of Medicine, Kyoto, and Department of Gastroeneterology and Hepatology, Kinki University Graduate School of Medicine, Osaka, Japan.
Kudo
Masatoshi
M
Chiba
Tsutomu
T
Wakatsuki
Yoshio
Y