|
|
Blood, 1 August 2008, Vol. 112, No. 3, pp. 916-917.
 Previous Article | Table of Contents | Next Article 
CORRESPONDENCE
Response: Decoy receptor 3 (DcR3), a pleiotropic immunomodulator
Roosneck et al speculated that "any protein carrying an HSPG binding domain fused to the Fc portion of IgG may achieve immunosuppression" based on their observation of the inhibitory effects of TACI-Fc versus BCMA-Fc, and Fc-APRIL versus its mutants Fc-APRIL-H98 and ACRP.Fc. They also speculated that this feature is likely to constitute an advantage to use TACI-Fc in autoimmune disorders. The first speculation is in accord with our observation that HBD.Fc, the recombinant protein comprising the heparan sulfate-binding domain (HBD) of DcR3 and Fc portion of human IgG1, functions as DcR3.Fc does to induce dendritic cell (DC) apoptosis.1 However, more experiments are needed to consolidate this argument, such as using recombinant proteins comprising the consensus sequences of HBD fused with IgG1.Fc to compare their effects with DcR3.Fc and HBD.Fc to induce DC apoptosis,1 modulate the differentiation and activation of DC and macrophage,2,3 activate PKC-delta,1,4 and enhance osteoclast differentiation.5 These experiments will provide information to support, or against, their second speculation.
No doubt oligomerized DcR3 is more potent than monomeric DcR3,3 and DcR3 fused with Fc or another tag might enhance DcR3 activity by increasing stability, dimerization, or oligomerization. However, endogenous DcR3 without Fc still has effects similar to DcR3.Fc because the modulatory effects of DcR3.Fc are also observed in transgenic mice overexpressing DcR3.6,7 Recently, we further demonstrated that DcR3.Fc is able to down-regulate the expression of the master regulator of MHC-II expression (CIITA) in tumor-associated macrophages (TAM) in vitro, and this is confirmed in the TAMs derived from transgenic mice and cancer patients with up-regulated DcR3.8 Therefore, like APRIL,9 endogenous DcR3 might be able to bind to extracellular matrix or to proteoglycan-positive cells to induce oligomerization, and is as potent as, or similar to, DcR3.Fc.
In addition to interacting with proteoglycan, DcR3 also interacts and neutralizes the functions of 3 members of the tumor necrosis factor (TNF) superfamily: Fas ligand (FasL),10 LIGHT,11 and TL1A.12 Previous studies have shown that DcR3 inhibits FasL-mediated apoptosis7 and enhance angiogenesis via neutralizing TL1A in vivo.13 Therefore, the newly identified action in DC apoptosis is one of the pleiotropic effects of DcR3 to promote tumor growth.
Several reports have shown that higher serum level of DcR3 correlates with poor prognosis of cancer patients,8,14–16 and the presence of DcR3 correlates with resistance to 5-fluorouracil–based adjuvant chemotherapy.17 Therefore, serum level of DcR3 is not only a useful marker to predict cancer prognosis, but is also an important parameter to predict tumor resistance to certain chemotherapy.
 |
Authorship
|
|---|
Conflict-of-interest disclosure: The author declares no competing financial interests.
Correspondence: Shie-Liang Hsieh, Professor, Department of Microbiology and Immunology, National Yang-Ming University, 155, Sec. 2, Li-Nong Street, Shih-Pai, Taipei, Taiwan 11211; e-mail: slhsieh{at}ym.edu.tw; slhsieh{at}gate.sinica.edu.tw.
Shie-Liang Hsieh
|
References
|
|---|
- You R-I, Chang YC, Chen PM, et al. Apoptosis of dendritic cells induced by decoy receptor 3 (DcR3). Blood. 2008;111:1480–1488.[Abstract/Free Full Text]
- Hsu TL, Chang YC, Chen SJ, et al. Modulation of dendritic cell differentiation and maturation by decoy receptor 3. J Immunol. 2002;168:4846–4853.[Abstract/Free Full Text]
- Chang YC, Hsu TL, Lin HH, et al. Modulation of macrophage differentiation and activation by decoy receptor 3. J Leukoc Biol. 2004;75:486–494.[Abstract/Free Full Text]
- Chang YC, Chan YH, Jackson DG, Hsieh SL. The glycosaminoglycan-binding domain of decoy receptor 3 is essential for induction of monocyte adhesion. J Immunol. 2006;176:173–180.[Abstract/Free Full Text]
- Tang CH, Hsu TL, Lin WW, et al. Attenuation of bone mass and increase of osteoclast formation in decoy receptor 3 transgenic mice. J Biol Chem. 2007;282:2346–2354.[Abstract/Free Full Text]
- Sung HH, Juang JH, Lin YC, et al. Transgenic expression of decoy receptor 3 protects islets from spontaneous and chemical-induced autoimmune destruction in nonobese diabetic mice. J Exp Med. 2004;199:1143–1151.[Abstract/Free Full Text]
- Hsu TL, Wu YY, Chang YC, et al. Attenuation of Th1 response in decoy receptor 3 transgenic mice. J Immunol. 2005;175:5135–5145.[Abstract/Free Full Text]
- Chang YC, Chen TC, Lee CT, et al. Epigenetic control of MHC-II expression in tumor-associated macrophages by decoy receptor 3. Blood. 2008;111:5054–5063.[Abstract/Free Full Text]
- Ingold K, Zumsteg A, Tardivel A, et al. Identification of proteoglycans as the APRIL-specific binding partners. J Exp Med. 2005;201:1375–1383.[Abstract/Free Full Text]
- Pitti RM, Marsters SA, Lawrence DA, et al. Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature. 1998;396:699–703.[CrossRef][Medline]
[Order article via Infotrieve]
- Yu KY, Kwon B, Ni J, Zhai Y, Ebner R, Kwon BS. A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis. J Biol Chem. 1999;274:13733–13736.[Abstract/Free Full Text]
- Migone TS, Zhang J, Luo X, et al. TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator. Immunity. 2002;16:479–492.[CrossRef][Medline]
[Order article via Infotrieve]
- Yang CR, Hsieh SL, Teng CM, Ho FM, Su WL, Lin WW. Soluble decoy receptor 3 induces angiogenesis by neutralization of TL1A, a cytokine belonging to tumor necrosis factor superfamily and exhibiting angiostatic action. Cancer Res. 2004;64:1122–1129.[Abstract/Free Full Text]
- Takahama Y, Yamada Y, Emoto K, et al. The prognostic significance of overexpression of the decoy receptor for Fas ligand (DcR3) in patients with gastric carcinomas. Gastric Cancer. 2002;5:61–68.[CrossRef][Medline]
[Order article via Infotrieve]
- Wu Y, Guo E, Yu J, Xie Q. High DcR3 expression predicts stage pN2-3 in gastric cancer. Am J Clin Oncol. 2008;31:79–83.[Medline]
[Order article via Infotrieve]
- Li H, Zhang L, Lou H, et al. Overexpression of decoy receptor 3 in precancerous lesions and adenocarcinoma of the esophagus. Am J Clin Pathol. 2005;124:282–287.[Abstract/Free Full Text]
- Mild G, Bachmann F, Boulay JL, et al. DcR3 locus is a predictive marker for 5-fluorouracil-based adjuvant chemotherapy in colorectal cancer. Int J Cancer. 2002;102:254–257.[CrossRef][Medline]
[Order article via Infotrieve]
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Articles in Blood Online:
-
Heparan sulfate proteoglycans, Fc receptors, and DC suppression
- Eddy Roosnek, Pascal Schneider, and Bertrand Huard
Blood 2008 112: 915-916.
[Full Text]
[PDF]
-
Apoptosis of dendritic cells induced by decoy receptor 3 (DcR3)
- Ren-In You, Yung-Chi Chang, Po-Min Chen, Wei-Shu Wang, Tsui-Ling Hsu, Chih-Ya Yang, Chun-Ting Lee, and Shie-Liang Hsieh
Blood 2008 111: 1480-1488.
[Abstract]
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
C.-Y. Chen, K.-Y. Yang, M.-Y. Chen, H.-Y. Chen, M.-T. Lin, Y.-C. Lee, R.-P. Perng, S.-L. Hsieh, P.-C. Yang, and T.-Y. Chou
Decoy Receptor 3 Levels in Peripheral Blood Predict Outcomes of Acute Respiratory Distress Syndrome
Am. J. Respir. Crit. Care Med.,
October 15, 2009;
180(8):
751 - 760.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
Top
Authorship
References