Invited Lecture(JSH)
Thu. November 2nd   9:00 - 9:30   Room 5: Portopia Hotel South Wing Ohwada A
Invited Lecture11
 The role of lymphatic vascular system in chronic liver diseases
Yasuko Iwakiri
Section of Digestive Diseases / Department of Internal Medicine, Yale School of Medicine
Hepatic lymphatic vessels play a key role in fluid homeostasis and mediate the transport of various immune cells, antigens, proteins and lipids to lymph nodes. Approximately 25-50% of lymph passing through the thoracic duct originates in the liver, making it the key organ for lymph production. While an increase in lymphatic vessel numbers (i.e., lymphangiogenesis) has been reported in chronic liver disease, the impact of lymphangiogenesis on liver pathophysiology remains incompletely understood (1-3). In diseases with inflammatory reaction, the symptoms are alleviated by increasing lymphatic vessels, but in intrahepatic bile duct cancer, and so on, it is possible to prevent metastasis by blocking lymphangiogenesis. In our study of hepatic encephalopathy in cirrhotic rats (4), local overexpression of VEGF-C in the brain using adeno-associated virus (AAV) promoted meningeal lymphangiogenesis and its drainage function, reduced inflammation of the brain parenchyma and improved motor function of rats. Lymphangiogenic therapy by controlling lymphangiogenesis and its function is expected to become a new treatment strategy for liver disease and its complications (1). In this lecture, the role of lymphatic vessels in chronic liver diseases and the possibility of treatment strategies for liver cirrhosis by targeting hepatic lymphatics will be discussed.

References:
1) Jeong, J., Tanaka, M. & Iwakiri, Y. Hepatic lymphatic vascular system in health and disease. J Hepatol 77, 206-218 (2022).
2) Tanaka, M. & Iwakiri, Y. Lymphatics in the liver. Curr Opin Immunol 53, 137-142 (2018).
3) Tanaka, M. & Iwakiri, Y. The Hepatic Lymphatic Vascular System: Structure, Function, Markers, and Lymphangiogenesis. Cell Mol Gastroenterol Hepatol 2, 733-749 (2016).
4) Hsu, S.J., Zhang, C., Jeong, J., Lee, S.I., McConnell, M., Utsumi, T. & Iwakiri, Y. Enhanced Meningeal Lymphatic Drainage Ameliorates Neuroinflammation and Hepatic Encephalopathy in Cirrhotic Rats. Gastroenterology 160, 1315-1329 e1313 (2021).
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