第三號誘餌受體在紅斑性狼瘡T細胞的活化及凋化所扮演之角色

Role of decoy receptor 3 (DcR3) in T cell activation and apoptosis in Systemic Lupus Erythematosus (SLE)

周詩茵(Shih-Yin Chou)

指導教授 ： 許秉寧

國立臺灣大學/醫學院/免疫學研究所/碩士(2004年)

https://doi.org/10.6342/NTU.2004.01136

摘要

第三號誘餌受體 (DcR3) 是一個新定義的分子，屬於腫瘤壞死因子受體家族中的一員,它是FasL，LIGHT和TL1A的受體。然而對於可溶性DcR3的生物角色並不清楚，最近有一些文獻發現在紅斑性狼瘡 (SLE) 病人可以看到DcR3 mRNA的過度表現。在我們的研究中證明相較於正常人，在SLE病人的血清中的確有看到明顯增高的DcR3蛋白質，暗示著DcR3可能在SLE病人的生理及病理機轉扮演著某種角色。為了探討DcR3在SLE中可能影響的病理機轉，我們想要研究DcR3是否可能直接引起T細胞的活化，並且是否可能抑制活化T細胞所引起的細胞自發性死亡。在我們的結果證明可溶性DcR3與低濃度下的plate-bound anti-CD3抗體共同刺激下，可以增強人類T細胞的增殖，並且促進IL-2和IFN-

關鍵字

T 細胞 ； 細胞凋亡 ； 第三誘餌受體 ； 紅斑性狼瘡

並列摘要

Decoy receptor 3 (DcR3), a newly member of tumor necrosis factor receptor (TNFR) superfamily, is a receptor for Fas ligand (FasL), LIGHT and TL1A. The biological role of soluble DcR3 is not clear, while DcR3 mRNA has been reported over-expressed in patients with systemic lupus erythematosus (SLE). Here we demonstrated marked elevated serum DcR3 in patients with SLE compared with normal health controls, suggested that DcR3 may play a role in SLE. In order to clarify the possible mechanisms in the pathogenesis of SLE by DcR3, we study whether DcR3 could directly induce T cell activation and whether it could promote survival of activated T cells via inhibiting the activation induced cell death (AICD). Our results demonstrated that soluble DcR3-Fc enhanced human T cell proliferation and increased production of IL-2 and IFN-

並列關鍵字

DcR3 ； SLE ； T cell ； apoptosis

參考文獻

Alderson, M. R., Tough, T. W., Davis-Smith, T., Braddy, S., Falk, B., Schooley, K. A., Goodwin, R. G., Smith, C. A., Ramsdell, F., and Lynch, D. H. (1995). Fas ligand mediates activation-induced cell death in human T lymphocytes. J Exp Med 181, 71-77.

Bai, C., Connolly, B., Metzker, M. L., Hilliard, C. A., Liu, X., Sandig, V., Soderman, A., Galloway, S. M., Liu, Q., Austin, C. P., and Caskey, C. T. (2000). Overexpression of M68/DcR3 in human gastrointestinal tract tumors independent of gene amplification and its location in a four-gene cluster. Proc Natl Acad Sci U S A 97, 1230-1235.

Blair, P. J., Riley, J. L., Harlan, D. M., Abe, R., Tadaki, D. K., Hoffmann, S. C., White, L., Francomano, T., Perfetto, S. J., Kirk, A. D., and June, C. H. (2000). CD40 ligand (CD154) triggers a short-term CD4(+) T cell activation response that results in secretion of immunomodulatory cytokines and apoptosis. J Exp Med 191, 651-660.

Blanco, P., Palucka, A. K., Gill, M., Pascual, V., and Banchereau, J. (2001). Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science 294, 1540-1543.

Brunner, F., Stessel, H., Watzinger, N., Loffler, B. M., and Opie, L. H. (1995). Binding of endothelin to plasma proteins and tissue receptors: effects on endothelin determination, vasoactivity, and tissue kinetics. FEBS Lett 373, 97-101.