HEPATITIS & LIVER DISEASES

Biography

Michel Samson has got his PhD in 1993 at University of Paris XI (France). He studied as postdoctoral scientist at Université Libre de Bruxelles (Brussels, Belgium) supported by prestigious fellowships (EMBO, European Community, etc..). He passed two years as visiting scientist at Genentech (California, USA). He is now team leader and director of research of Inserm at University of Rennes (France) in UMR 1085 Inserm, vice-director of Institut de Recherche en Santé, Environnement et Travail. He studies the inflammation, cell death and fibrosis in liver pathologies.  He has published more than 90 papers in reputed journals (Nature, Cell, J Exp Med, Hepatology, J Hepatol., etc...), with already more than 8850 citations and H-index 38.

Abstract

Hepatocyte death is a starting point of liver disease progression by promoting inflammatory and regenerative processes. The death of hepatocytes can be induced by the large variety of immune, infectious and toxic agents. The molecular mechanisms regulating these cell death pathways are poorly documented. Innate and acquired immune cells play key roles in the induction or amplification of hepatolysis, mainly mediated by expression and release of death ligands belonging to the TNF-superfamily including TNF-α, FasL and TRAIL.  In this study, we investigated the role of RIPK1, a protein known to regulate cell fate decisions, in the death of hepatocytes using different in vivo models of hepatitis. Acute hepatitis was induced in mice by Concanavalin A (ConA), lipopolysaccharide (LPS), DNA-CpG, recombinant IFN-γ and TRAIL co-administration, FASL, Poly I:C and Murine-Hepatitis virus type 3. Using specific conditional mice deficient in RIPK1 only in liver parenchymal cells (LPC) (Ripk1^LPC-KO), we reveal its necessary function in the protection of hepatocyte during hepatitis. Administration of lipsome-encapsulated Cl2MBP served to investigate the role of Kupffer cells in the establishment of the disease. Moreover, Etanercept, a TNF-decoy receptor, was used to study the contribution of TNF-α during liver injury. All together, these works demonstrate that deletion of RIPK1 sensitizes hepatocytes to TNF-α-induced apoptosis. Thus RIPK1 plays a key role in the protection of hepatocytes during acute and chronic hepatitis.