AYURVEDIC ALTERNATIVES IN AUTOIMMUNITY

描述（由申请人提供）：用于治疗系统性自身免疫性疾病的常规药物通常与长期副作用相关。这刺激了对这些疾病的替代或补充治疗方式的研究，包括系统性红斑狼疮。基于它对其他几种慢性疾病的疗效，作为阿育吠陀的补充，姜黄素在治疗狼疮方面有很大的希望——然而，这从未被直接测试过。我们最近在小鼠模型中发现了狼疮发展过程中至少3个主要的检查点——淋巴细胞对自身抗原耐受的破坏，过度活跃的促炎树突状细胞对自身免疫过程的放大，以及终末器官炎症，特别是对肾脏的影响。基因简化的小鼠模型最近被生成，包含了这些单独的检查点。这项应用的目的是利用这些新的遗传模型来了解姜黄素是否以及如何影响免疫耐受、树突状细胞功能和/或终末器官炎症。剖析自身免疫替代治疗方案的作用机制将使我们最终优化狼疮的补充治疗策略，根据患者的基因组成量身定制。

DESCRIPTION (provided by applicant): Conventional medications for the management of systemic autoimmune diseases are often associated with long-term side-effects. This has spurred research into alternative or complementary treatment modalities for these diseases, including systemic lupus erythematosus. Based on its efficacy in several other chronic diseases, the Ayurvedic supplement, curcumin holds great promise in lupus treatment - however, this has never been tested directly. Our recent work in mouse models has uncovered at least 3 major checkpoints in lupus development - breach in lymphocyte tolerance to self antigens, amplification of the autoimmune process by hyperactive, pro-inflammatory dendritic cells, and end-organ inflammation, affecting the kidneys in particular. Genetically simplified mouse models have recently been generated, encompassing these individual checkpoints. The goal of this application is to use these novel genetic models to understand if and how curcumin might impact immune tolerance, dendritic cell function and/or end-organ inflammation. Dissecting out the mechanism of action of alternative therapeutic regimes in autoimmunity will allow us to eventually optimize complementary treatment strategies for lupus, tailored to the genetic makeup of the patient. PUBLIC HEALTH RELEVANCE: Conventional medications for the management of SLE are often associated with long- term side-effects. In this context, "natural supplements" may be particularly useful if proven effective. Based on its efficacy in several other chronic diseases, the Ayurvedic supplement, curcumin holds great promise in lupus treatment. The proposed studies will ascertain the precise check-points and mechanisms of action through which curcumin might work in lupus. The findings from this study could have a profound impact on how we use natural supplements in treating human SLE in the future.