[Frontiers in Bioscience E1, 99-114, June 1, 2009]

Dendritic cell immunobiology in relation to liver transplant outcome

Tina L. Sumpter1,2, John G. Lunz III1,3, Antonino Castellaneta1,2, Benjamin Matta1,2,4, Daisuke Tokita1,2, Heth R. Turnquist1,2, George V. Mazariegos1,2, A. Jake Demetris1,3, Angus W. Thomson1,2,4

1Starzl Transplantation Institute and Departments of 2Surgery, 3Pathology and 4Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, BST W1540, Pittsburgh, PA 1526


2. Introduction
3. Immunobiology of liver DC
3.1. Phenotypic characteristics of DC
3.2. DC migration in and out of the liver
3.3. DC-T cell interactions
3.4. Liver DC: relative resistance to LPS-induced stimulation
3.5. DC and liver transplant outcome
4. Molecular regulation of liver DC signaling/maturation
5. DC-NK/NKT cell interactions
6. Liver regeneration and DC function
7. Influence of viral hepatitis and liver cancer on DC function
7.1. Viral hepatis and impairment of DC function
7.2. Liver cancer, functional modification of DC and immunotolerance
8. Impact of anti-inflammatory and immunosuppressive agents on DC function
9. Acknowledgments
10. References


The unique immunologic environment of the liver, together with its anatomic location downstream of the gut, influences the maturation and function of its interstitial dendritic cell (DC) populations. These well-equipped, antigen-presenting cells play critical roles in regulation of innate and adaptive immunity. New information is emerging about the molecular regulation of liver DC maturation and function, and their tolerogenic potential, while new insight is being gained regarding interactions between liver DC and other immune effector cell populations (NK, NKT cells) in addition to T cells. During transplantation, factors that affect liver DC biology include ischemia-reperfusion injury, liver regeneration, viral infection and the actions of anti-inflammatory and immunosuppressive drugs. Herein, we review the molecular and cell biology of hepatic DC populations in relation to the regulation of alloimmune responses and liver transplant outcome.