Murine Model of Familial Hemophagocytic Lymphohistiocytosis Hepatitis is Mediated by IFN-γ in a Predominantly Hepatic-Intrinsic Manner

Interferon gamma (IFN-γ) is the main cytokine driving Familial Hemophagocytic Lymphohistiocytosis (FHL) organ dysfunction. Hepatocytes are known to have IFN-γ receptor (IFN-γ-R). Blockade of IFN-γ pathway ameliorates FHL hepatitis, in animal models and in humans. However, whether IFN-γ induced hepatitis in FHL is a lymphocyte or liver intrinsic response to the cytokine has yet to be elucidated. We report that IFN-γ-mediated hepatic injury in the murine model of FHL is caused by direct effect on the liver and has a necessary role in recruitment of the inflammatory mediators of injury in FHL: inflammatory monocytes and CD8+ effector memory T lymphocytes (CD8+ CD44hi CD62Llo) (Tem). Fresh mouse liver segments were stored in RNAlater® solution (Thermo Fisher Scientific) at -20°C and thawed for RNA extraction at later date. RNA extraction was performed in livers of 4 mice from the BM IFNgR+/+ and host IFNgR -/- group and 4 mice from the BM IFNgR+/+ and host IFNgR+/+ group using the Qiagen RNeasy Mini Kit protocol from approximately 30mg of homogenized tissue according to manufacturer instructions.