Tolerizing DNA vaccines for autoimmune arthritis
Tolerizing DNA vaccines for autoimmune arthritis
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DOI：
10.1080/08916930601061603
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发表时间：
2006-12-01
期刊：
影响因子：
3.5
通讯作者：
Robinson, William H.
中科院分区：
文献类型：
--
作者：
Ho, Peggy P.;Higgins, John P.;Robinson, William H.
目前用于类风湿性关节炎（RA）和其他自身免疫性疾病的疗法非特异性地抑制免疫功能，并且非常需要基本方法，例如抗原特异性耐受化疗法。在本文中，我们描述了开发抗原特异性耐受DNA疫苗来治疗小鼠胶原诱导的关节炎（CIA），并使用蛋白质微阵列来监测对治疗的反应，并确定下一代疫苗的潜在额外的自身免疫靶点。我们证明，耐受编码II型胶原（CII）的DNA疫苗降低了CIA的发病率和严重程度。阿托伐他汀是一种他汀类药物，可降低自身免疫的严重程度，增强编码CII的DNA疫苗的作用。与对照疫苗相比，由来自接受编码CII的耐受性DNA的小鼠的胶原反应性T细胞产生的细胞因子的分析揭示了促炎细胞因子IFN-γ和TNF-α的产生减少。关节炎微阵列分析表明，在用编码CII的DNA治疗的小鼠中，自身抗体应答的扩散减少。开发耐受性DNA疫苗，以及使用抗体谱来指导设计和监测对此类疫苗的治疗反应，代表了治疗RA和其他自身免疫性疾病的有希望的方法。
Current therapies for rheumatoid arthritis ( RA) and other autoimmune diseases non-specifically suppress immune function, and there is great need for fundamental approaches such as antigen-specific tolerizing therapy. In this paper we describe development of antigen-specific tolerizing DNA vaccines to treat collagen-induced arthritis ( CIA) in mice, and use of protein microarrays to monitor response to therapy and to identify potential additional autoimmune targets for next generation vaccines. We demonstrate that tolerizing DNA vaccines encoding type II collagen ( CII) reduced the incidence and severity of CIA. Atorvastatin, a statin drug found to reduce the severity of autoimmunity, potentiated the effect of DNA vaccines encoding CII. Analysis of cytokines produced by collagen-reactive T cells derived from mice receiving tolerizing DNA encoding CII, as compared to control vaccines, revealed reduced production of the pro-inflammatory cytokines IFN-gamma and TNF-alpha. Arthritis microarray analysis demonstrated reduced spreading of autoantibody responses in mice treated with DNA encoding CII. The development of tolerizing DNA vaccines, and the use of antibody profiling to guide design of and to monitor therapeutic responses to such vaccines, represents a promising approach for the treatment of RA and other autoimmune diseases.