Th229 - ZFYVE21 Is a Mediator of Inflammatory Liver Disease

Quan Jiang, PhD; Shaoxun Wang, PhD – Yale University; Qianxun Wang – Yale University; Song Guiyu, MD, PhD – Yale University; Mahsa Nouri Barkestani, PhD – Yale University; Dan Jane-wit, MD, PhD – Yale University

Abstract Text: Non-alcoholic steatohepatitis (NASH) is characterized by lipotoxicity and hepatic inflammation and predisposes patients to hepatocellular carcinoma. The immune mechanisms underlying NASH are undefined, hindering the development of therapeutics. We have identified an early endosome effector, ZFYVE21, that, when knocked out in endothelial cells in mice, elicits NASH by 3 months of age. Livers from these mice show signs of endothelial cell dysfunction and upregulate a broad panel of pro-inflammatory mediators including CCL5, a known mediator of NASH. Endothelial cell-specific ZFYVE21 regulates inflammatory processes associated with NASH.