| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Laboratory of Transplantation Immunology and
Nephrology Service of Notre Dame Hospital, Centre Hospitalier de l’Université de Montréal, Université de Montréal, Montreal, Quebec, Canada;
Department of Surgery, Second Affiliated Hospital of the Zhejiang Medical College, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; and
Human Genome Sciences Inc., Rockville, MD 20850
TR6/DcR3 is a secreted molecule belonging to the TNFR family. Its ligands are LIGHT, Fas ligand, and TL1A, all TNF family members. TR6 is expressed in some tumors and is hypothesized to endow tumor cells with survival advantages by blocking Fas-mediated apoptosis. It can also inhibit T cell activation by interfering with two-way T cell costimulation between LIGHT and HveA. In this study, we discovered a novel function of TR6: inhibition of T cell chemotaxis. Human T cells pretreated with soluble or solid-phase TR6-Fc showed compromised migration toward CXCL12/stromal cell-derived factor 1
in vitro in a Transwell assay. Such an effect could also be observed in T cells pretreated with soluble or solid-phase HveA-Fc or anti-LIGHT mAb, suggesting that LIGHT reverse signaling was likely responsible for chemotaxis inhibition. TR6 pretreatment also led to T cell chemotaxis suppression in vivo in the mice, confirming in vivo relevance of the in vitro observation. Mechanistically, a small GTPase Cdc42 failed to be activated after TR6 pretreatment of human T cells, and further downstream, p38 mitogen-activated protein kinase activation, actin polymerization, and pseudopodium formation were all down-regulated in the treated T cells. This study revealed a previously unknown function of TR6 in immune regulation, and such an effect could conceivably be explored for therapeutic use in controlling undesirable immune responses.
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]
|
|
|
|
 |
|
 H.-F. Chen, J.-S. Chen, C.-T. Shun, Y.-F. Tsai, and H.-N. Ho Decoy receptor 3 expression during the menstrual cycle and pregnancy, and regulation by sex steroids in endometrial cells in vitro Hum. Reprod., June 1, 2009; 24(6): 1350 - 1358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B Funke, F Autschbach, S Kim, F Lasitschka, U Strauch, G Rogler, G Gdynia, L Li, N Gretz, S Macher-Goeppinger, et al. Functional characterisation of decoy receptor 3 in Crohn's disease Gut, April 1, 2009; 58(4): 483 - 491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-H. Chen and C.-R. Yang Decoy Receptor 3 Expression in AsPC-1 Human Pancreatic Adenocarcinoma Cells via the Phosphatidylinositol 3-Kinase-, Akt-, and NF-{kappa}B-Dependent Pathway J. Immunol., December 15, 2008; 181(12): 8441 - 8449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Han, R. Bojalil, L. M. Amezcua-Guerra, R. Springall, H. Valderrama-Carvajal, J. Wu, and H. Luo DcR3 as a diagnostic parameter and risk factor for systemic lupus erythematosus Int. Immunol., August 1, 2008; 20(8): 1067 - 1075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Terra, H. Luo, X. Qiao, and J. Wu Tissue-specific expression of B-cell translocation gene 2 (BTG2) and its function in T-cell immune responses in a transgenic mouse model Int. Immunol., March 1, 2008; 20(3): 317 - 326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-M. Ka, H.-K. Sytwu, D.-M. Chang, S.-L. Hsieh, P.-Y. Tsai, and A. Chen Decoy Receptor 3 Ameliorates an Autoimmune Crescentic Glomerulonephritis Model in Mice J. Am. Soc. Nephrol., September 1, 2007; 18(9): 2473 - 2485. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Bendall, R. Baraz, J. Juarez, W. Shen, and K. F. Bradstock Defective p38 Mitogen-Activated Protein Kinase Signaling Impairs Chemotaxic but not Proliferative Responses to Stromal-Derived Factor-1{alpha} in Acute Lymphoblastic Leukemia Cancer Res., April 15, 2005; 65(8): 3290 - 3298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Shi, J. Mao, G. Yu, J. Zhang, and J. Wu Tumor Vaccine Based on Cell Surface Expression of DcR3/TR6 J. Immunol., April 15, 2005; 174(8): 4727 - 4735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Levine Mechanisms of Soluble Cytokine Receptor Generation J. Immunol., November 1, 2004; 173(9): 5343 - 5348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Y. Wu, Y.-C. Chang, T.-L. Hsu, S.-L. Hsieh, and M.-Z. Lai Sensitization of Cells to TRAIL-induced Apoptosis by Decoy Receptor 3 J. Biol. Chem., October 15, 2004; 279(42): 44211 - 44218. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-H. Sung, J.-H. Juang, Y.-C. Lin, C.-H. Kuo, J.-T. Hung, A. Chen, D.-M. Chang, S.-Y. Chang, S.-L. Hsieh, and H.-K. Sytwu Transgenic Expression of Decoy Receptor 3 Protects Islets from Spontaneous and Chemical-induced Autoimmune Destruction in Nonobese Diabetic Mice J. Exp. Med., April 19, 2004; 199(8): 1143 - 1151. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
