Decoy receptor 3: A pleiotropic immunomodulator and biomarker for inflammatory diseases, autoimmune diseases and cancer
Journal
Biochemical Pharmacology
Journal Volume
81
Journal Issue
7
Pages
838-847
Date Issued
2011
Author(s)
Hsieh S.-L.
Abstract
Recently, several decoy molecules belonging to tumor necrosis factor receptor superfamily (TNFRSF) have been identified, including decoy receptor 1 (DcR1), decoy receptor 2 (DcR2), and decoy receptor 3 (DcR3). One of the tumor necrosis factor superfamily (TNFSF) members, TNF-related apoptosis-inducing ligand (TRAIL), binds to DcR1 and DcR2, which are membranous receptors with a truncated cytoplasmic domain, thus unable to transduce TRAIL-mediated signaling. In contrast to DcR1 and DcR2, DcR3 is a soluble receptor capable of neutralizing the biological effects of three other TNFSF members: Fas ligand (FasL/TNFSF6/CD95L), LIGHT (TNFSF14) and TNF-like molecule 1A (TL1A/TNFSF15). Since FasL is a potent apoptosis- and inflammation-inducing factor, LIGHT is involved in apoptosis and inflammation, and TL1A is a T cell costimulator and is involved in gut inflammation, DcR3 can be defined as an immunomodulator on the basis of its neutralizing effects on FasL, LIGHT, and TL1A. Initial studies demonstrated that DcR3 expression is elevated in tumors cells; however, later work showed that DcR3 expression is also upregulated in inflammatory diseases, where serum DcR3 levels correlate with disease progression. In addition to its neutralizing effect, DcR3 also acts as an effector molecule to modulate cell function via 'non-decoy' activities. This review focuses on the immunomodulatory effects of DcR3 via 'decoy' and 'non-decoy' functions, and discusses the potential of DcR3 as a biomarker to predict cancer invasion and inflammation progression. We also discuss the possible utility of recombinant DcR3 as a therapeutic agent to control autoimmune diseases, as well as the potential to attenuate tumor progression by inhibiting DcR3 expression. ? 2011 Elsevier Inc. All rights reserved.
SDGs
Other Subjects
actin; biological marker; decoy receptor 3; decoy receptor 3 immunoglobulin Fc fragment; Fas antigen; Fas ligand; immunoglobulin enhancer binding protein; immunomodulating agent; LIGHT protein; lymphotoxin beta receptor; major histocompatibility antigen class 2; proteoheparan sulfate; tumor necrosis factor like molecule 1A; tumor necrosis factor like molecule 1A antagonist; tumor necrosis factor receptor; tumor necrosis factor related apoptosis inducing ligand; unclassified drug; apoptosis; autoimmune disease; cancer cell; cancer invasion; cell adhesion; cell differentiation; collagen induced arthritis; DcR3 gene; dendritic cell; disease marker; enteritis; enzyme inhibition; epigenetics; Epstein Barr virus; gene expression; gene function; graft rejection; homeostasis; human; immunomodulation; immunopathogenesis; inflammation; inflammatory disease; insulin dependent diabetes mellitus; keratinocyte; kidney disease; macrophage; malignant neoplastic disease; monocyte; multiple sclerosis; nonhuman; note; nucleotide sequence; osteoclast; ovary; pleiotropy; priority journal; protein assembly; protein expression; rheumatoid arthritis; sensitization; testis; Th2 cell; transcription regulation; tumor associated leukocyte; tumor gene; tumor growth; upregulation; Autoimmune Diseases; Biological Markers; Humans; Inflammation; Ligands; Neoplasms; Receptors, Tumor Necrosis Factor, Member 6b
Type
note