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

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posted on 2023-05-18, 12:20 authored by Anand, S, Wang, P, Yoshimura, K, Choi, I-H, Hillard, A, Chen, YH, Wang, C-R, Schulick, R, Andrew FliesAndrew Flies, Zhu, G, Xu, Y, Pardoll, DM, Chen, L, Tamada, K
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.

History

Publication title

Journal of Clinical Investigation

Volume

116

Issue

4

Pagination

1045-1051

ISSN

0021-9738

Department/School

Menzies Institute for Medical Research

Publisher

American Society for Clinical Investigation

Place of publication

United States

Rights statement

© 2006, The American Society for Clinical Investigation.

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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