Forkhead box p3+ regulatory T cell underlies male resistance to experimental type 2 autoimmune hepatitis

Pascal Lapierre, Kathie Béland, Caroline Martin, Fernando Alvarez, Fernando Alvarez – 22 April 2010 – Autoimmune hepatitis (AIH), like many autoimmune diseases, is most prevalent in young women. The immunological basis of this age and sex susceptibility bias was investigated in a murine model of AIH. Xenoimmunization of 7‐week‐old female C57BL/6 mice resulted in more severe AIH with higher levels of liver inflammation, serum alanine aminotransferase, specific T‐cell cytotoxicity, and autoantibody than younger and older females.

Hepatitis B virus activates deoxynucleotide synthesis in nondividing hepatocytes by targeting the R2 gene

Dorit Cohen, Yaarit Adamovich, Nina Reuven, Yosef Shaul – 22 April 2010 – Hepatitis B virus (HBV) causes liver diseases from acute hepatitis to cirrhosis and liver cancer. Currently, more than 350 million people are chronic HBV carriers, with devastating prognosis. HBV is a small enveloped noncytopathic virus, containing a circular partially double‐stranded DNA genome, and exhibits strong tropism for human liver cells. Infected individuals (acute and chronic) secrete about 107 to 1011 virions per day to the bloodstream, with each infected cell releasing 50‐300 viruses per day.

The utility of genome‐wide association studies in hepatology

Tom H. Karlsen, Espen Melum, Andre Franke – 22 April 2010 – Over the last 4 years, more than 450 genome‐wide association studies (GWAS) have been successfully performed in a variety of human traits, of which approximately 2% relates to the field of hepatology. Whereas the many robust susceptibility gene findings have provided insight into fundamental physiological aspects of the phenotypes that have been studied, the widespread application has also revealed important limitations of the GWAS design.

Mammalian target of rapamycin regulates vascular endothelial growth factor–dependent liver cyst growth in polycystin‐2–defective mice

Carlo Spirli, Stefano Okolicsanyi, Romina Fiorotto, Luca Fabris, Massimiliano Cadamuro, Silvia Lecchi, Xin Tian, Stefan Somlo, Mario Strazzabosco – 22 April 2010 – Polycystic liver disease may complicate autosomal dominant polycystic kidney disease (ADPKD), a disease caused by mutations in polycystins, which are proteins that regulate signaling, morphogenesis, and differentiation in epithelial cells. The cystic biliary epithelium [liver cystic epithelium (LCE)] secretes vascular endothelial growth factor (VEGF), which promotes liver cyst growth via autocrine and paracrine mechanisms.

Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development

Thomas Touboul, Nicholas R. F. Hannan, Sébastien Corbineau, Amélie Martinez, Clémence Martinet, Sophie Branchereau, Sylvie Mainot, Hélène Strick‐Marchand, Roger Pedersen, James Di Santo, Anne Weber, Ludovic Vallier – 22 April 2010 – Generation of hepatocytes from human embryonic stem cells (hESCs) could represent an advantageous source of cells for cell therapy approaches as an alternative to orthotopic liver transplantation. However, the generation of differentiated hepatocytes from hESCs remains a major challenge, especially using a method compatible with clinical applications.

Deletion of CD39 on natural killer cells attenuates hepatic ischemia/reperfusion injury in mice

Guido Beldi, Yara Banz, Alexander Kroemer, Xiaofeng Sun, Yan Wu, Nadine Graubardt, Alyssa Rellstab, Martina Nowak, Keiichi Enjyoji, Xian Li, Wolfgang G. Junger, Daniel Candinas, Simon C. Robson – 22 April 2010 – Natural killer (NK) cells play crucial roles in innate immunity and express CD39 (Ecto‐nucleoside triphosphate diphosphohydrolase 1 [E‐NTPD1]), a rate‐limiting ectonucleotidase in the phosphohydrolysis of extracellular nucleotides to adenosine.

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