Mueller André M, Pedré Xiomara, Killian Stephan, David Monique, Steinbrecher Andreas
Department of Neurology, University of Regensburg, Regensburg, Germany.
J Neuroimmunol. 2009 Apr 30;209(1-2):57-64. doi: 10.1016/j.jneuroim.2009.01.024. Epub 2009 Mar 6.
The Decoy Receptor 3 (DcR3) is known to compete with the signalling receptors of the Fas ligand (FasL), LIGHT and the TNF-like molecule 1A (TL1A). The primary aim of this study was to provide insights into the role of DcR3 in the modulation of myelin-specific encephalitogenic autoimmune T cell responses. Treatment of PLP-specific lymph node cells with DcR3.Fc protein resulted in a suppression of IFN-g and IL-17, in a reduced proportion of Th17 cells and in a decrease of encephalitogenicity. The Th17 response promoting cytokines IL-6 and IL-23 were suppressed by DcR3.Fc as well. DcR3.Fc-treatment of CD4+ T cells with a defective FasL did not influence the production of IL-17 indicating that DcR3 suppresses IL-17 production by disruption of Fas-FasL interactions. We identified high concentrations of DcR3 in the cerebrospinal fluid (CSF) of patients with various neurological disease states while almost no DcR3 was detected in corresponding serum samples. In conclusion, DcR3 modulates CNS-autoimmunity by interfering with Th17 responses via blockade of Fas-FasL interaction. The anti-inflammatory properties and high DcR3 concentrations in the CSF warrant further investigations in the expression pattern and the function of DcR3 within the CNS.
诱饵受体3（DcR3）已知可与Fas配体（FasL）、LIGHT和TNF样分子1A（TL1A）的信号受体竞争。本研究的主要目的是深入了解DcR3在调节髓鞘特异性致脑炎性自身免疫性T细胞反应中的作用。用DcR3.Fc蛋白处理PLP特异性淋巴结细胞可导致IFN-γ和IL-17受到抑制，Th17细胞比例降低，致脑炎性减弱。促进Th17反应的细胞因子IL-6和IL-23也被DcR3.Fc抑制。用DcR3.Fc处理FasL缺陷的CD4+T细胞不会影响IL-17的产生，这表明DcR3通过破坏Fas-FasL相互作用来抑制IL-17的产生。我们在患有各种神经疾病状态的患者的脑脊液（CSF）中发现了高浓度的DcR3，而在相应的血清样本中几乎未检测到DcR3。总之，DcR3通过阻断Fas-FasL相互作用干扰Th17反应来调节中枢神经系统自身免疫。脑脊液中DcR3的抗炎特性和高浓度值得进一步研究其在中枢神经系统中的表达模式和功能。
