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一种通过先天性和适应性免疫系统治疗自身免疫性疾病的免疫调节性GpG寡核苷酸。

An immunomodulatory GpG oligonucleotide for the treatment of autoimmunity via the innate and adaptive immune systems.

作者信息

Ho Peggy P, Fontoura Paulo, Ruiz Pedro J, Steinman Lawrence, Garren Hideki

机构信息

Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Beckman Center for Molecular Medicine, Stanford, CA 94305-5316, USA.

出版信息

J Immunol. 2003 Nov 1;171(9):4920-6. doi: 10.4049/jimmunol.171.9.4920.

Abstract

Bacterial DNA and immunostimulatory CpG oligodeoxynucleotides (ODNs) activate the innate immune system to produce proinflammatory cytokines. Shown to be potent Th1-like adjuvants, stimulatory CpG motifs are currently used as effective therapeutic vaccines for various animal models of infectious diseases, tumors, allergies, and autoimmune diseases. In this study, we show that the application of an immunomodulatory GpG ODN, with a single base switch from CpG to GpG, can effectively inhibit the activation of Th1 T cells associated with autoimmune disease. Moreover, this immunomodulatory GpG ODN suppresses the severity of experimental autoimmune encephalomyelitis in mice, a prototypic Th1-mediated animal disease model for multiple sclerosis.

摘要

细菌DNA和免疫刺激的CpG寡脱氧核苷酸(ODN)可激活先天免疫系统以产生促炎细胞因子。具有刺激作用的CpG基序被证明是强效的Th1样佐剂,目前被用作针对各种传染病、肿瘤、过敏和自身免疫性疾病动物模型的有效治疗性疫苗。在本研究中,我们表明,应用一种免疫调节性GpG ODN(通过将CpG中的一个碱基替换为GpG)可有效抑制与自身免疫性疾病相关的Th1 T细胞的激活。此外,这种免疫调节性GpG ODN可减轻小鼠实验性自身免疫性脑脊髓炎的严重程度,该疾病是多发性硬化症的一种典型的Th1介导的动物疾病模型。

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