Decoy receptor 3: A pleiotropic immunomodulator and biomarker for inflammatory diseases, autoimmune diseases and cancer

Lin, Wan-Wan; Hsieh, Shie Liang

doi:10.1016/j.bcp.2011.01.011

Cited by 141 publications

(137 citation statements)

References 95 publications

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“…Several investigators reported that both the glycosaminoglycan HA and the decoy receptor DcR3 could be key players in tumor development (33)(34)(35)(36)(37). It was demonstrated that HA is released by tumor cells and blocks the inflammatory signaling in human monocytes (34, 37); DcR3 can be defined as an immunomodulator on the basis of its neu- tralizing effects on FasL, LIGHT, and TL1A.…”

Section: Soluble Factors With Putative Involvement In the Observed Etmentioning

confidence: 99%

“…It was demonstrated that HA is released by tumor cells and blocks the inflammatory signaling in human monocytes (34, 37); DcR3 can be defined as an immunomodulator on the basis of its neu- tralizing effects on FasL, LIGHT, and TL1A. Initial studies demonstrated that DcR3 expression is elevated in tumor cells; however, later work showed that DcR3 expression is also upregulated in inflammatory diseases (35,36). Thus, we decided to study the putative role of these soluble factors in the development of the observed ET in CLL.…”

Section: Soluble Factors With Putative Involvement In the Observed Etmentioning

confidence: 99%

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Chronic Lymphocytic Leukemia: A Paradigm of Innate Immune Cross-Tolerance

Jurado-Camino

Esteban-Burgos

Hernández-Jiménez

et al. 2015

The Journal of Immunology

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Infections are a significant cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). The pathogenesis of infections is multifactorial and includes hypogammaglobulinemia, conventional therapy with alkylating drugs, and recently, purine analogs and mAb-associated T cells. Patients without these risk factors also suffer from infections, although the mechanism remains unknown. In a cohort of 70 patients with CLL, we demonstrated that their monocytes were locked into a refractory state and were unable to mount a classic inflammatory response to pathogens. In addition, they exhibited the primary features of endotoxin tolerance, including low cytokine production, high phagocytic activity, and impaired Ag presentation. The involvement of miR-146a in this phenomenon was suspected. We found miR-146a target genes, such as IRAK1 and TRAF6, were manifestly downregulated. Our study provides a new explanation for infections in patients with CLL and describes a cross-tolerance between endotoxins and tumors.

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Section: Soluble Factors With Putative Involvement In the Observed Etmentioning

confidence: 99%

Section: Soluble Factors With Putative Involvement In the Observed Etmentioning

confidence: 99%

Chronic Lymphocytic Leukemia: A Paradigm of Innate Immune Cross-Tolerance

Jurado-Camino

Esteban-Burgos

Hernández-Jiménez

et al. 2015

The Journal of Immunology

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“…[8][9][10] Overexpression of TNFRSF6B, originally found in lung and colon cancers and virus-associated lymphoma, is capable of protecting cancer cells against apoptosis. 11 Mounting evidences have shown that TNFRSF6B overexpression is a novel tissue biomarker for predicting tumor invasion and worsening of various chronic inflammatory diseases. 11 Serum TNFRSF6B level is markedly elevated in patients with chronic kidney disease, 12 and our recent study has shown that serum TNFRSF6B is an inflammatory biomarker and associates with mortality in hemodialysis patients.…”

mentioning

confidence: 99%

“…11 Mounting evidences have shown that TNFRSF6B overexpression is a novel tissue biomarker for predicting tumor invasion and worsening of various chronic inflammatory diseases. 11 Serum TNFRSF6B level is markedly elevated in patients with chronic kidney disease, 12 and our recent study has shown that serum TNFRSF6B is an inflammatory biomarker and associates with mortality in hemodialysis patients. 13 In human tissues, TNFRSF6B is normally expressed in the colon, stomach, spleen, lymph nodes, and lung but not in kidneys.…”

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confidence: 99%

Expression of TNFRSF6B in kidneys is a novel predictor for progression of chronic kidney disease

Tseng

Yang

et al. 2013

Modern Pathology

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TNFRSF6B overexpression in tumors is a novel predictor for poor prognosis in various cancers; however, whether TNFRSF6B could be expressed in kidney tissues of patients with chronic kidney disease is unknown. Current established risk factors cannot fully predict the progression of chronic kidney disease, and, therefore, it is mandatory to develop a newer marker for predicting disease progression. We conducted a prospective cohort study comprised 167 patients with chronic kidney disease undergoing renal biopsy at a tertiary hospital with median follow-up of 30.5 months. Computer-assisted quantitative immunohistochemical staining analysis of TNFRSF6B in kidney tissues, the expression of a-smooth muscle actin and percentage of fibrosis in renal interstitium, estimated glomerular filtration rate, and urinary protein excretion rate were investigated. Study endpoint was a doubling of serum creatinine and/or end-stage renal failure requiring renal replacement therapy. We found that TNFRSF6B was predominantly expressed in the tubular epithelial cells of renal cortex. The higher the expression of TNFRSF6B, the more the expression of a-smooth muscle actin and fibrosis in interstitium (Po0.001). Forty patients reaching endpoint had lower baseline estimated glomerular filtration rate and higher expression of TNFRSF6B in renal tubular epithelial cells. Multivariate Cox regression analysis showed that high expression of TNFRSF6B independently predicted the risk toward the renal endpoint with a hazard ratio of 3.46 (95% confidence interval (CI) 1.76-6.80, Po0.001) by adjusting for clinical and pathologic variables. While added to a model of estimated glomerular filtration rate, proteinuria and other conventional risk factors, TNFRSF6B further significantly improved the model predictability for progression of chronic kidney disease (area under the curve, 0.82). In conclusion, TNFRSF6B is associated with renal fibrosis and high expression of TNFRSF6B is a novel biomarker for predicting the progression of chronic kidney disease. Modern Pathology (2013) 26, 984-994;

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“…The gene encoding DcR3 produces a 300-aa polypeptide, and it is found in humans but not in mice. DcR3 is barely detectable in normal tissues; however, it is overexpressed in a variety of tumor cells such as adenocarcinomas of the esophagus, stomach, colon, rectum, and pancreas (1)(2)(3)(4) and in lymphomas and gliomas (5,6). Earlier reports showed that DcR3 binds to Fas ligand (FasL), homologous to lymphotoxin, showing inducible expression, and competing with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes (LIGHT), and TNF-like molecule 1A (TL1A) (1,7,8).…”

mentioning

confidence: 99%

Decoy Receptor 3 Suppresses TLR2-Mediated B Cell Activation by Targeting NF-κB

Huang¹,

Kang²,

Chen³

et al. 2012

The Journal of Immunology

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Decoy receptor 3 (DcR3) is a soluble protein in the TNFR superfamily. Its known ligands include Fas ligand, homologous to lymphotoxin, showing inducible expression, and competing with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes, TNF-like molecule 1A, and heparan sulfate proteoglycans. DcR3 has been reported to modulate the functions of T cells, dendritic cells, and macrophages; however, its role in regulating B cell activation is largely unknown. In this study, we found that the DcR3.Fc fusion protein bound to human and mouse B cells and suppressed the activation of B cells. DcR3.Fc attenuated Staphylococcus aureus, IgM-, Pam3CSK4-, and LPS-mediated B cell proliferation but did not affect cytokine-induced B cell growth. In the presence of these mitogens, DcR3.Fc did not induce B cell apoptosis, suggesting that DcR3 may inhibit the signal(s) important for B cell activation. Because the combination of Fas.Fc, LT-βR.Fc (homologous to lymphotoxin, showing inducible expression, and competing with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes receptor), and DR3.Fc (TNF-like molecule 1A receptor) did not suppress B cell proliferation and because the biological effect of DcR3.Fc on B cells was not blocked by heparin, we hypothesize that a novel ligand(s) of DcR3 mediates its inhibitory activity on B cells. Moreover, we found that TLR2-stimulated NF-κB p65 activation and NF-κB–driven luciferase activity were attenuated by DcR3.Fc. The TLR2-induced cytokine production by B cells was consistently reduced by DcR3. These results imply that DcR3 may regulate B cell activation by suppressing the activation of NF-κB.

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Decoy receptor 3: A pleiotropic immunomodulator and biomarker for inflammatory diseases, autoimmune diseases and cancer

Cited by 141 publications

References 95 publications

Chronic Lymphocytic Leukemia: A Paradigm of Innate Immune Cross-Tolerance

Chronic Lymphocytic Leukemia: A Paradigm of Innate Immune Cross-Tolerance

Expression of TNFRSF6B in kidneys is a novel predictor for progression of chronic kidney disease

Decoy Receptor 3 Suppresses TLR2-Mediated B Cell Activation by Targeting NF-κB

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