Hepatitis Research Today is a free monthly online journal that collates and summarizes the latest research about Hepatitis, including details on hepatitis a, b, c, causes, symptoms. | ||||||||
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Essential role of TNF family molecule LIGHT as a cytokine in the pathogenesis of hepatitis.Anand S, Wang P, Yoshimura K, Choi IH, Hilliard A, Chen YH, Wang CR, Schulick R, Flies AS, Flies DB, Zhu G, Xu Y, Pardoll DM, Chen L, Tamada K Immunology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. LIGHT is an important costimulatory molecule for T cell immunity. Recent studies have further implicated its role in innate immunity and inflammatory diseases, but its cellular and molecular mechanisms remain elusive. We report here that LIGHT is upregulated and functions as a proinflammatory cytokine in 2 independent experimental hepatitis models, induced by concanavalin A and Listeria monocytogenes. Molecular mutagenesis studies suggest that soluble LIGHT protein produced by cleavage from the cell membrane plays an important role in this effect through the interaction with the lymphotoxin-beta receptor (LTbetaR) but not herpes virus entry mediator. NK1.1+ T cells contribute to the production, but not the cleavage or effector functions, of soluble LIGHT. Importantly, treatment with a mAb that specifically interferes with the LIGHT-LTbetaR interaction protects mice from lethal hepatitis. Our studies thus identify a what we believe to be a novel function of soluble LIGHT in vivo and offer a potential target for therapeutic interventions in hepatic inflammatory diseases. Published 4 April 2006 in J Clin Invest, 116(4): 1045-51.
© 2006-2008 Hepatitis Research Today. All Rights Reserved. |
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