Research

To maintain immune homeostasis, the liver has evolved redundant regulatory strategies. The focus of my research is to understand the cellular and molecular immunological events in the liver.

We created and use a mouse liver transplant model capable of detecting the interaction between T cells and antigen-presenting cells under the influences of liver environmental factors. We have shown that the inherent tolerogenicity of liver transplants could be owing to the organ’s combination of hematopoietic activity, production of growth factors and immunoregulatory cytokines, unique population of resident cells, and relatively large numbers of potentially tolerogenic antigen-presenting cells.

We reported the existence of sublineages of dendritic cells (DCs) in the liver, which influence the generation of proinflammatory responses and contribute to tolerance. Both the environments and intrinsic properties of these cell lineages dictate the quantity and quality of immune responses in normal or disease states.

We recently found immunoregulatory activities of liver stellate cells (SCs), known to be involved in repairing and regenerating the liver. Following activation by IFN-g or direct contact with activated T cells, SCs upregulate many death-inducing molecules (PD-L1, TRAIL), produce inhibitory cytokines (IL-10, TGF-β and IL-6) and growth factors (HGF, VEGF), leading to inhibition of immune responses. This was confirmed by protection of islet allografts by co-transplanted SCs.

Future studies will focus on mechanisms by which T cells/DCs/SCs interact in regulating liver immunity.