Decoy receptor 3: Its role as biomarker for chronic inflammatory diseases

Members of the tumor-necrosis factor-α (TNF-α) and TNF-α receptor (TNFR) superfamilies of proteins (TNFSF and TNFRSF, respectively) play important roles in the function of the immune system. Decoy receptor 3 (DcR3, TNFRSF6b) is a decoy receptor that binds to three TNFSF ligands, FasL, LIGHT and TL1A. Association to these ligands competes with the corresponding functional receptors and blocks downstream signaling, leading to immunomodulatory effects, including the prevention of apoptosis. DcR3 lacks a transmembrane region and exists only as a secreted protein, which is detectable in biological fluids. Recent studies have shown that DcR3 is upregulated and may be pathogenetically implicated in several and diverse chronic inflammatory diseases. The strongest associations have been described for rheumatological diseases, mainly systemic lupus erythematosus and rheumatoid arthritis, inflammatory bowel disease, and serious infectious conditions, including systemic inflammatory response syndrome. In the majority of these conditions, DcR3 mRNA and protein expression is elevated both at the target tissues as well as in the systemic circulation. DcR3 concentration in the serum is untraceable in the majority of healthy individuals but can be detected in patients with various inflammatory diseases. In most such cases, soluble DcR3 correlates with disease severity, as patients with severe forms of disease have significantly higher levels than patients with milder or no activity. In addition, effective anti-inflammatory treatment leads to the disappearance of soluble DcR3 from the circulation. Taken together, current evidence suggests that serum DcR3 may become a useful biomarker for chronic inflammatory disorders, as it is upregulated in response to inflammatory stimuli, and may serve both as a prognostic marker for disease severity and as a surrogate indicator of response to treatment.