IMR Press / FBL / Volume 9 / Issue 3 / DOI: 10.2741/1395

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
The role of TWEAK/Fn14 in the pathogenesis of inflammation and systemic autoimmunity
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1 The Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461
2 The Department of Exploratory Science, Biogen Idec, 12 Cambridge Center, Cambridge, MA 02142
3 The Ruth and Irving Claremon Research Laboratory, Division of Rheumatology/Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461
Academic Editor:Linda Spatz
Front. Biosci. (Landmark Ed) 2004, 9(3), 2273–2284; https://doi.org/10.2741/1395
Published: 1 September 2004
(This article belongs to the Special Issue Mechanisms for the maintenance and the breakdown of B cell tolerance)
Abstract

Interactions between members of the TNF ligand superfamily with their cognate TNF receptors play a crucial role in maintaining immune homeostasis in normal individuals, while dysregulation of certain TNF-ligands and receptors contributes to the pathogenesis of autoimmunity. Identification of novel members of the TNF ligand and receptor families will promote our understanding of the pathogenesis of systemic autoimmune diseases, thus facilitating the development of novel therapeutic approaches. TNF-like weak inducer of apoptosis (TWEAK), a recently identified member of the TNF ligand family, induces PGE2, MMP-1, IL-6, IL-8, RANTES, and IP-10 in fibroblasts and synoviocytes, and upregulates ICAM-1, E-selectin, IL-8, and MCP-1 in endothelial cells. The receptor for TWEAK, Fn14, is expressed in various organs including the kidney; it is intriguing that some of these chemokines induced by TWEAK are crucial in the pathogenesis of lupus nephritis. Furthermore, others have described upregulated TWEAK expression on the surface of T cells in human lupus. In this paper we review the possible roles of TWEAK/TWEAK receptor interactions in the pathogenesis of inflammatory and systemic autoimmune diseases, with particular focus on systemic lupus erythematosus. TWEAK blockade may be helpful therapeutically in restoration of tolerance, but is more likely to modify inflammatory damage in target organs.

Keywords
TNF family members
TWEAK
Fn14
Apoptosis
SLE
chemokines
Lupus nephritis
CNS lupus
Review
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