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Essential role of TNF family molecule LIGHT as a cytokine in the pathogenesis of hepatitis

Citation

Anand, S and Wang, P and Yoshimura, K and Choi, I-H and Hillard, A and Chen, YH and Wang, C-R and Schulick, R and Flies, AS and Zhu, G and Xu, Y and Pardoll, DM and Chen, L and Tamada, K, Essential role of TNF family molecule LIGHT as a cytokine in the pathogenesis of hepatitis, Journal of Clinical Investigation, 116, (4) pp. 1045-1051. ISSN 0021-9738 (2006) [Refereed Article]


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Copyright Statement

2006, The American Society for Clinical Investigation.

DOI: doi:10.1172/JCI27083

Abstract

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.

Item Details

Item Type:Refereed Article
Keywords:immunology
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Cellular Immunology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
Author:Flies, AS (Dr Andy Flies)
ID Code:102358
Year Published:2006
Web of Science® Times Cited:53
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-08-16
Last Modified:2016-11-02
Downloads:118 View Download Statistics

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