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Targeting the LIGHT-HVEM Pathway

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Therapeutic Targets of the TNF Superfamily

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 647))

Abstract

Tumor necrosis factor (TNF)-related cytokines function as key communication systems between cells of the immune system and mediate inflammation and tissue destruction. LIGHT (TNFSF14) is a key component of the communication system that controls the responses of T-Cells. LIGHT activates two cell surface receptors, the Herpesvirus Entry Mediator (HVEM) and the Lymphotoxin-β Receptor and is inhibited by soluble decoy receptor-3. The LIGHT-HVEM pathway is an important cosignaling pathway for T-Cells, whereas LIGHT-LTβR modifies the functions of dendritic cells and stromal cells by creating tissue microenvironments, which promote immune responses. HVEM also binds an Ig superfamily member, B and T lymphocyte attenuator (BTLA) that inhibits T-Cell activation. Thus, HVEM serves as a molecular switch between stimulatory and inhibitory signaling. Studies in humans and experimental animal models reveal that LIGHT contributes to inflammation and pathogenesis in mucosal, hepatic, joint and vascular tissues. LIGHT is accessible to biologic-based therapeutics, which can be used to target this molecule during inflammation-driven diseases.

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Author information

Authors and Affiliations

  1. Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California, 92037, USA

    Carl F. Ware

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  1. Carl F. Ware
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Editors and Affiliations

  1. Department of Preclinical Therapeutics, Seattle Genetics, Inc., Bothell, Washington, USA

    Iqbal S. Grewal PhD

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© 2009 Landes Bioscience and Springer Science+Business Media

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Ware, C.F. (2009). Targeting the LIGHT-HVEM Pathway. In: Grewal, I.S. (eds) Therapeutic Targets of the TNF Superfamily. Advances in Experimental Medicine and Biology, vol 647. Springer, New York, NY. https://doi.org/10.1007/978-0-387-89520-8_10

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