Hepatocytes mediate Notch dependent immune regulation in response to inflammation in the regenerating mouse liver

Objective: A single injection of concanavalin A (ConA) to mice induces acute Th1-mediated hepatitis. Tolerance against ConA rechallenge develops within 8 days and is mediated by IL-10 predominantly produced by CD4+CD25+Foxp3+ regulatory T cells (Tregs) and Kupffer Cells. This study was intended to identify the role of hepatocytes (HC) in ConA-induced immunoregulation. Methods: HC or splenic DC were isolated from saline- or ConA-pretreated wt, IL-10-, IFNγ-, or interferon regulatory factor (IRF)-1-deficient mice. Subsequently, HC or DC were co-cultured with splenic CD4+ T cells from wt, DEREG or IL-10 KO mice and…