Our research program has been focusing on investigation of the mechanisms involved in regulation of liver immunity in context of liver inflammatory diseases and liver transplant. Active regulation of the immune response in the liver favors the development of peripheral tolerance and maintaining liver homeostasis, which are associated with chronic hepatic infections and cancer metastasis. We demonstrated that the hepatic stellate cells (HSC), a unique population of Retinoid-storing hepatic tissue cells, play an important regulatory role in alloantigen-induced immune responses through their direct impact on T cell differentiation / survival and indirect impact on immune responses via generation myeloid derived suppressive cells (MDSC). We have created a mouse authotopic liver transplantation model and HSC/islet co-transplantation model to investigate the molecular and cellular mechanisms involved.Taking advantage of the availabilities of many transgenic and knockout mouse lines, these models provides a unique tool for us to understand immune responses regulated by liver tissue cells, in particular HSC. We have reported that INFg signaling is absolutely required for immune regulation by HSC. In the inflamed environment, the activated HSC markedly upregulate suppressive molecule expressions on their surface and release multiple factors, which contribute to attenuation of CD8 T cell activation and expansion of MDSC, consequently leading to tolerance. Understanding of the underlying mechanisms will help us to develop novel strategies for substantial improvement of transplant outcomes and for treatmetn of chronic viral infection in the liver.

Coming soon.

  1. Chou H-S, Hsieh C-C, Charles R, Wang L, Wagner T, Fung JJ, Qian S and Lu L. Protect Islet Transplants via B7-H1 Mediated Enhancement of T Regulatory Cells. Transplantation, 2012, 93: 272-282.
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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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