Direct, help‐independent priming of CD8+ T cells by adeno‐associated virus–transduced hepatocytes

Sherry A. Wuensch, Jessica Spahn, Ian N. Crispe – 26 August 2010 – Both hepatitis B and C viruses frequently establish chronic infection, raising the question whether T cells are poorly primed in the liver. To determine the role of different cell types in the activation of CD8+ T cells against hepatocellular antigens, we used an Adeno‐associated virus to deliver ovalbumin to hepatocytes. In contrast to CD8+ T cells, CD4+ T cells were not activated.

A novel monoclonal antibody to characterize pathogenic polymers in liver disease associated with α1‐antitrypsin deficiency

Elena Miranda, Juan Pérez, Ugo I. Ekeowa, Nedim Hadzic, Noor Kalsheker, Bibek Gooptu, Bernard Portmann, Didier Belorgey, Marian Hill, Susan Chambers, Jeff Teckman, Graeme J. Alexander, Stefan J. Marciniak, David A. Lomas – 26 August 2010 – Alpha1‐antitrypsin is the most abundant circulating protease inhibitor. The severe Z deficiency allele (Glu342Lys) causes the protein to undergo a conformational transition and form ordered polymers that are retained within hepatocytes. This causes neonatal hepatitis, cirrhosis, and hepatocellular carcinoma.

Lectin complement pathway gene profile of donor and recipient determine the risk of bacterial infections after orthotopic liver transplantation

Bert‐Jan F. de Rooij, Bart van Hoek, W. Rogier ten Hove, Anja Roos, Lee H. Bouwman, Alexander F. Schaapherder, Robert J. Porte, Mohamed R. Daha, Johan J. van der Reijden, Minneke J. Coenraad, Jan Ringers, Andrzej G. Baranski, Bouke G. Hepkema, Daniel W. Hommes, Hein W. Verspaget – 26 August 2010 – Infectious complications after orthotopic liver transplantation (OLT) are a major clinical problem. The lectin pathway of complement activation is liver‐derived and a crucial effector of the innate immune defense against pathogens.

A multifaceted imbalance of T cells with regulatory function characterizes type 1 autoimmune hepatitis

Silvia Ferri, Maria Serena Longhi, Chiara De Molo, Claudine Lalanne, Paolo Muratori, Alessandro Granito, Munther J. Hussain, Yun Ma, Marco Lenzi, Giorgina Mieli‐Vergani, Francesco B. Bianchi, Diego Vergani, Luigi Muratori – 26 August 2010 – Immunotolerance is maintained by regulatory T cells (Tregs), including CD4+CD25hi, CD8+CD28−, γδ, and CD3+CD56+ [natural killer T (NKT)] cells. CD4+CD25hi cells are impaired in children with autoimmune hepatitis (AIH). Little is known about Tregs in adults with AIH.

Histone deacetylase inhibition suppresses the transforming growth factor β1–induced epithelial‐to‐mesenchymal transition in hepatocytes

Aki Kaimori, James J. Potter, Michael Choti, Zhen Ding, Esteban Mezey, Ayman A. Koteish – 26 August 2010 – Transforming growth factor β1 (TGFβ1) plays a crucial role in the induction of the epithelial‐to‐mesenchymal transition (EMT) in hepatocytes, which contributes to the pathogenesis of liver fibrosis. The inhibition of the TGFβ1 cascade suppresses EMT and the resultant fibrosis. In this study, we focus on EMT‐induced fibrosis in hepatocytes and the epigenetic regulation of the type I collagen gene.

Beneficial paracrine effects of cannabinoid receptor 2 on liver injury and regeneration

Fatima Teixeira‐Clerc, Marie‐Pierre Belot, Sylvie Manin, Vanessa Deveaux, Thomas Cadoudal, Marie‐Noele Chobert, Alexandre Louvet, Andreas Zimmer, Thierry Tordjmann, Ariane Mallat, Sophie Lotersztajn – 26 August 2010 – The cannabinoid receptor 2 (CB2) plays a pleiotropic role in innate immunity and is a crucial mediator of liver disease. In this study, we investigated the impact of CB2 receptors on the regenerative process associated with liver injury.

Suppression of liver regeneration and hepatocyte proliferation in hepatocyte‐targeted glypican 3 transgenic mice

Bowen Liu, Aaron W. Bell, Shirish Paranjpe, William C. Bowen, Jaspal S. Khillan, Jian‐Hua Luo, Wendy M. Mars, George K. Michalopoulos – 26 August 2010 – Glypican 3 (GPC3) belongs to a family of glycosylphosphatidylinositol‐anchored, cell‐surface heparan sulfate proteoglycans. GPC3 is overexpressed in hepatocellular carcinoma. Loss‐of‐function mutations of GPC3 result in Simpson‐Golabi‐Behmel syndrome, an X‐linked disorder characterized by overgrowth of multiple organs, including the liver.

Direct activation of forkhead box O3 by tumor suppressors p53 and p73 is disrupted during liver regeneration in mice

Svitlana Kurinna, Sabrina A. Stratton, Wen‐Wei Tsai, Kadir C. Akdemir, Weisong Gu, Pallavi Singh, Triona Goode, Gretchen J. Darlington, Michelle Craig Barton – 26 August 2010 – The p53 family of proteins regulates the expression of target genes that promote cell cycle arrest and apoptosis, which may be linked to cellular growth control as well as tumor suppression. Within the p53 family, p53 and the transactivating p73 isoform (TA‐p73) have hepatic‐specific functions in development and tumor suppression.

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