Current program
- Liver dendritic cells regulate hepatic immunity
- Immunosuppressive activity of hepatic stellate cells
- Prevention of hemophilia A inhibitors by administration of tolerogenic
dendritic cells
Brief Description
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-ß 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.
Publications
Chou H-S, Hsieh C-C, Yang H-R, Wang L, Arakawa Y, Brown K, Wu Q, Lin F, Peters M, Fung JJ, Qian S, Lu L: Hepatic Stellate Cells Regulate Immune Response via Induction of Myeloid Suppressor Cells. Hepatology, 2011, 53:1007-1019
Zhidan Tua, QingLi Hong-ShiueChou, Ching-ChuangHsieh, Howard Meyerson,Marion G.Peterse, Hong Bu, John J Fung, Shiguang Qian, Feng Lin and Lina Lu: Complement mediated hepatocytes injury in a model of autoantibody induced hepatitis. Immunobiology, 2011, 216:528-534
David G. Lott, Olivia Dan, Marshall Strome and Lina Lu: Decoy NF-kB fortified immature dendritic cells maintain laryngeal allograft integrity and provide enhancement of regulatory T Cells. The Laryngoscope, 2010, 120:44-52
Miwa Morita, Masayuki Fujino, Guoping Jiang, John Fung, Shiguang Qian, Xiao-Kang Li and Lina Lu: PD1/B7H1 interaction contributes to the spontaneous acceptance of liver allograft. American Journal of Transplantation, 2010,10:40-46
Jungmee Kang, Gabor Erdodi, Joseph P. Kennedy, Hongshiue Chou, Lina Lu, Sharon Grundfest: Broniatowski. Toward a bioartificial pancreas: Diffusion of insulin and IgG across immuno-protective membranes with controlled hydrophilic channel diameters. Macromolecular Bioscience 2010 10:369-377
Liqiao Zhou, Tong Zhu1, Bing Wang, Xiaoyan Liang, Lina Lu, and Xiao Xiao: Long-term protection against HPV E7-positive tumor by a single vaccination of AAV vectors encoding a fusion protein of inactivated E7 of HPV 16/18 and heat shock protein 70. Human Gene Therapy, 2010, 21: 109 -119
Ragni M, Wu W, Liang X, Hsieh CC, Cortese-Hassett A, and Lu L: Factor VIII-Pulsed Dendritic Cells Reduce Anti-F.VIII Antibody Formation in the Hemophilia A Mouse Model. Experimental Hematology 2009, 37:744-754
Yang HR, Hsieh X, Chou H, Brown K, Fung J, Qian S and Lu L: Mechanistic Insights into Immunomodulation by Hepatic Stellate Cells in Mice: A Critical Role of Interferon-? Signaling. Hepatology, 2009, 50: 1981-1991
Grundfest-Broniatowski S, Tellioglu G, Rosenthal K A, Kang J, Erdodi G, Yalcin B, Cakmak M, Drazba J, Bennett A, Lu L and Kennedy J: A new bioartificial pancreas utilizing amphiphilic membranes for the immunoisolation of porcine islets: a pilot study in the canine. ASAIO Journal, 2009, 55:400-405
Jian G, Yang HR, Fung JJ, Qian S, and Lu L: Hepatic Stellate Cells Selectively Expand Allogeneic CD4+CD25+FoxP3+ Regulatory T Cells in an IL-2 Dependent Manner, Transplantation 2008, 86:1492-1502
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