An Investigation into a Protective Role of Regulatory T Cells in Acute Liver Failure (II, III)

Acute liver failure is a condition in which rapid deterioration of liver function results in high mortality. Currently, overall survival without transplantation is more than 95% in Taiwan. Furthermore, the lack of donor liver and the nature of rapid deterioration of this disease restrain the possibility for liver transplantation. Therefore, an effective treatment strategy except liver transplantation is urgently demanded. By our preliminary data, we have shown that the percentage of regulatory T cells increased in patients with acute liver failure. We also showed the tissue-protecting regulatory T cells (Treg cell) could rescue the mice from liver failure in an animal model of acetaminophen-induced hepatotoxicity which had been documented to be results of over-activation of innate immunity. Furthermore, by the animal model of HA specific regulatory T cell system, Rag-2 knockout mice and some other gene knockout systems, we have the advantage to explore mechanisms of these tissue-protecting Treg cells in restraining the liver inflammation. We will try to investigate the following issues: (I) to clarify the role of tissue-protecting Treg cells in an animal model of acute liver failure; (II) to clarify the cellular mechanisms of tissue-protecting Treg cells in this animal model; (III) to clarify the molecular mechanisms of tissue-protecting Treg cells in this animal model. By this approach, we expected to achieve the following accomplishments: (I). Extend the knowledge about the tissue-protective role of Treg cells; this could provide an important aspect of Treg cells and give some insight for the pathogenesis of autoimmune disease, transplantation immunology and viral immunology. (II). Extend the knowledge for the suppression mechanisms of Treg cell on innate immunity; this could provide an important knowledge for manipulating the Treg cell suppression function in order to develop immunotherapy for several disease. (III). Extend the knowledge about the liver immunology; this could provide some important observation for not only acute liver failure but also viral hepatitis and liver cancer. (IV) Provide a new treatment strategy for acute liver failure by in-vitro expansion of tissue-protecting Treg cells.

Project ID:PC9801-2582
External Project ID:NSC97-2314-B182-040-MY2