TRAIL Death Receptor-4, Decoy Receptor-1 and Decoy Receptor-2 Expression on CD8+ T Cells Correlate with the Disease Severity in Patients with Rheumatoid Arthritis

Abstract

BackgroundRheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disorder. Although the pathogenesis of disease is unclear, it is well known that T cells play a major role in both development and perpetuation of RA through activating macrophages and B cells. Since the lack of TNF-Related Apoptosis Inducing Ligand (TRAIL) expression resulted in defective thymocyte apoptosis leading to an autoimmune disease, we explored evidence for alterations in TRAIL/TRAIL receptor expression on peripheral T lymphocytes in the molecular mechanism of RA development.MethodsThe expression of TRAIL/TRAIL receptors on T cells in 20 RA patients and 12 control individuals were analyzed using flow cytometry. The correlation of TRAIL and its receptor expression profile was compared with clinical RA parameters (RA activity scored as per DAS28) using Spearman Rho Analysis.ResultsWhile no change was detected in the ratio of CD4+ to CD8+ T cells between controls and RA patient groups, upregulation of TRAIL and its receptors (both death and decoy) was detected on both CD4+ and CD8+ T cells in RA patients compared to control individuals. Death Receptor-4 (DR4) and the decoy receptors DcR1 and DcR2 on CD8+ T cells, but not on CD4+ T cells, were positively correlated with patients' DAS scores.ConclusionsOur data suggest that TRAIL/TRAIL receptor expression profiles on T cells might be important in revelation of RA pathogenesis.

sTRAIL Serum Levels and TRAIL 1595 Genotypes: Associations with Progress and Prognosis of Colorectal Carcinoma

“…Soluble form of this death ligand is also known to be biologically active and involved in the pathophysiology of different disease states such as cancer, viral infections, autoimmune diseases and inflammation [17,18,[20][21][22][23][24]. Polymorphisms of TRAIL gene was related with a variety of diseases so far.…”

An apoptosis-independent role of TRAIL in suppressing joint inflammation and inhibiting T-cell activation in inflammatory arthritis

“…been reported to be associated with the RA disease activity. 18 In addition to triggering apoptosis, recent evidence has suggested that TRAIL may have a role in T-cell homeostasis and the regulation of immune responses to viral infections and autoimmune diseases. 15,35 The inhibitory effect of TRAIL on T-cell activation was also observed in T cells, particularly the CD8 + population, that had infiltrated synovial fluid of RA patients.…”

“…16 In addition, TRAIL inhibits the development of autoimmune diabetes in non-obese diabetic (NOD) mice by inhibiting the proliferation of NOD diabetogenic T cells. 14 Patients with inflammation associated with rheumatoid arthritis (RA) demonstrate an increased level of the TRAIL receptor that is associated with the T-cell subsets and clinical scores, 17,18 and treatment with TRAIL reduces the severity of joint inflammation in an animal model of inflammatory arthritis, 19 which suggests that TRAIL may have a role in RA. However, the mechanism by which TRAIL regulates inflammatory arthritis is still unclear.…”

Rheumatoid arthritis in the elderly and its relationship with periodontitis: A review

“…In both RA, as well as periodontitis, either a decrease in expression of TRAIL death receptors or an increase in expression of TRAIL decoy receptor or a reduced sensitivity of inflammatory cells to TRAIL induced apoptosis results in an abnormally high concentration of these cells instigating excessive bone loss …”