Immune Modulation of Autoimmunity by Herbal Products

描述（由申请人提供）：根据5年前的调查，每年至少有36%的美国成年人采用某种形式的补充和替代医学（CAM）治疗来满足他们的医疗需求（2002年美国疾病控制与预防中心的全国访谈健康调查）。在CAM模式中，使用天然生长的植物产品作为有效的治疗实体，以及与传统使用的药物相比，草药相对缺乏毒性，使植物配方的消费在西方世界得到普及。尽管草药被广泛使用，但大多数草药的作用机制仍不清楚。我们利用自身免疫实验模型进行的初步研究表明，中草药雷公藤对临床疾病有抑制作用，并诱导抗原特异性免疫反应发生显著变化（如细胞因子反应从促炎型向抗炎型偏离，抗原特异性抗体的产生增加）。在本研究中，我们提出了通过CD4+CD25+ T调节细胞（Treg）、淋巴细胞进入靶器官的体内运输、保护性抗体和炎症介质来深入测试celastrus诱导免疫调节的机制。在这方面，我们的提案非常符合RFA-AT-08-003的目标。目的1。研究CD4+CD25+T细胞的抑制作用，从而导致celastrus喂养大鼠疾病过程的下调。目标2。目的：探讨龙葵减少潜在致病性T细胞向靶器官迁移的机制。目标3。确定增强抗体对疾病相关抗原的反应如何导致自身免疫反应的抑制。目标4。目的：检测雷公藤诱导炎症介质在靶组织中的调节作用。虽然这一建议涉及一种CAM模式（一种中草药）和一种自身免疫的实验模型，但我们相信我们研究阐明的基本机制原理也部分适用于其他CAM模式和其他自身免疫模型。

DESCRIPTION (provided by applicant): At least 36 percent of adult Americans adopted some form of complementary and alternative medicine (CAM) therapy for their healthcare needs annually as surveyed 5 years ago (National Interview Health Survey of 2002, CDC). Among CAM modalities, the use of naturally grown plant products as efficacious therapeutic entities as well as the relative lack of toxicity of herbs compared to conventionally used drugs has popularized the consumption of botanical formulas in the western world. Despite the extensive use of medicinal herbs, the mechanisms of action remain unclear for most of them. Our preliminary study using an experimental model of autoimmunity has revealed that the Chinese herb Celastrus suppresses clinical disease and induces significant changes in antigen-specific immune response (e.g., deviation of the cytokine response from pro-inflammatory to anti-inflammatory type, and increased production of antigenspecific antibodies). In this study, we have proposed experiments to test the in-depth mechanisms of Celastrus-induced immune modulation operative via the CD4+CD25+ T regulatory cells (Treg), the in vivo trafficking of lymphocytes into the target organ, the protective antibodies, and the inflammatory mediators. In this respect, our proposal is an excellent match with the objectives of RFA-AT-08-003. Aim 1. To study the suppressive function of CD4+CD25+T cells that leads to the downregulation of the disease process in Celastrus-fed rats. Aim 2. To examine the mechanisms by which Celastrus reduces the migration of potentially pathogenic T cells into the target organ. Aim 3. To determine how enhanced antibody response to the disease-related antigen leads to suppression of the autoimmune response. Aim 4. To test for the Celastrus-induced modulation of inflammatory mediators in the target tissue. Although this proposal involves one CAM modality (a Chinese herb) and one experimental model of autoimmunity, we believe that the basic mechanistic principles elucidated in our study would also be applicable in part to other CAM modalities as well as other models of autoimmunity. Public Health Relevance: Natural plant products are increasingly being used by patients with a variety of autoimmune diseases, such as diabetes, multiple sclerosis, arthritis and lupus. However, the mechanisms of action of many of these products are not defined. We propose to study the immune system related mechanisms by which Celastrus, a Chinese herb, mediates its beneficial effects against autoimmunity. We will conduct these studies in an experimental model of autoimmunity. The results of our study would help developing rationally designed therapeutic approaches for autoimmunity using botanical products.