Essential role of TNF family molecule LIGHT as a cytokine in the pathogenesis of hepatitis
2006
LIGHT is an important costimulatory molecule for T cell immunity. Recent studies have further implicated its
role in innate immunity and inflammatory diseases, butits 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-β receptor (LTβR) 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-LTβR 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.
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