Targeting the LIGHT-HVEM pathway.

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-beta Receptor and is inhibited by soluble decoy receptor-3. The LIGHT-HVEM pathway is an important cosignaling pathway for T-Cells, whereas LIGHT-LTbetaR 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.

• Authors: Carl F Ware
• Journal: Advances in experimental medicine and biology (Adv Exp Med Biol) Vol. 647 Pg. 146-55 ( 2009) ISSN: 0065-2598 [Print] United States
• PMID: 19760072 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

• Receptors, Tumor Necrosis Factor, Member 14
• Tumor Necrosis Factor Ligand Superfamily Member 14

Topics

• Animals
• Autoimmune Diseases (immunology, therapy)
• Humans
• Receptors, Tumor Necrosis Factor, Member 14 (antagonists & inhibitors, metabolism)
• Signal Transduction
• Tumor Necrosis Factor Ligand Superfamily Member 14 (antagonists & inhibitors, metabolism)
• Vascular Diseases (immunology, therapy)