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Suppression of Collagen Induced Arthritis with Altered Peptide Ligands

Suppression of Collagen Induced Arthritis with Altered Peptide Ligands
用改变的肽配体抑制胶原诱导的关节炎
批准号:
7578745
负责人:
ANDREW H KANG
金额:
$37.0万
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-09-01 至 2011-08-31

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中文摘要
翻译
类风湿性关节炎是一种慢性腹泻关节炎症性疾病。这 全身性疾病的特征是慢性滑膜炎,由抗原驱动的 针对软骨中发现的一种或多种蛋白质的免疫过程。尽管有几个 抗原被认为与类风湿性关节炎II型自身免疫反应有关。 胶原蛋白(CII)作为一种候选自身抗原备受关注。胶原蛋白诱导 关节炎(CIA)是一种实验性模型,与RA和IS有几个相似之处 用CII免疫敏感品系的小鼠所诱导的。我们已经使用了 建立CIA动物模型以开发选择性阻断的特异性免疫疗法 自身免疫,而不干扰免疫系统的有益功能。 在此之前,我们已经确定并描述了CII上的主要决定因素 被T细胞识别,并表明关节炎可以通过一种类似物来抑制 多肽(A9),它与野生型决定簇不同,有三个氨基酸。我们 假设A9类似肽发挥作用的一个主要机制是 驱使未表型的CD4T细胞具有独特的抑制表型。不像 最近描述的Treg细胞,A9诱导的抑制性T细胞亚群的特征是 FcRɣ表达增加,通过另一条途径(即Syk而不是 而不是ZAP-70),并主要分泌IL-4。为了进一步探索这一假说, 我们提出了以下具体目标:1)确定A9的结构特征 负责调节对CII和CIA的免疫反应。2) A9诱导的抑制性T细胞的特征我们认为一个决定性的 了解A9抑制关节炎的机制(S)将有助于 类风湿性关节炎的改进治疗方法的发展。
英文摘要
Rheumatoid arthritis is a chronic inflammatory disease of diarthrodial joints. This systemic disease is characterized by chronic synovitis, sustained by an antigen-driven immune process against one or more proteins found in cartilage. Although several antigens have been proposed to be involved in the autoimmune response in RA, type II collagen (CII) has received the most attention as a candidate autoantigen. Collageninduced arthritis (CIA) is an experimental model with several similarities to RA and is induced by immunization of susceptible strains of mice with CII. We have used the animal model of CIA to develop a specific immunotherapy capable of selectively blocking autoimmunity without interfering with the beneficial functions of the immune system. Previously we have identified and characterized the dominant determinant on CII recognized by T cells and have shown that arthritis can be suppressed by an analog peptide (A9), which differs from the wild-type determinant by three amino acids. We hypothesize that a major mechanism by which the A9 analog peptide functions is to drive uncommitted CD4+ T cells toward a unique inhibitory phenotype. Unlike the recently described Treg cells, the A9-induced inhibitory T cell subset is characterized by increased expression of FcRɣ, signaling through an alternate pathway (i.e. Syk rather than Zap-70), and secretion of predominantly IL-4. To further explore the hypothesis, we propose the following Specific Aims: 1) Identify the structural characteristics of A9 that are responsible for modulation of the immune response to CII and CIA. 2) Characterize the inhibitory T cells induced by A9 It is our belief that a definitive understanding of the mechanism(s) through which A9 suppresses arthritis will facilitate the development of improved treatments for RA.
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Novel Methods for Dissolving Blood Clots
  • 批准号:
    9063997
  • 项目类别:
  • 资助金额:
    $0.5万
  • 财政年份:
    2015
  • 负责人:
    ANDREW H KANG
  • 依托单位:
20(OH) Vit D3, T Cells, and Arthritis
20(OH) Vit D3, T Cells, and Arthritis
20(OH) Vit D3, T Cells, and Arthritis
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