The role of IL-2 therapy for Relapsing-Remitting Chikungunya Arthritis

摘要 基孔肯雅病毒（CHIKV）是一种由蚊子传播的甲病毒，可导致慢性关节炎。 约四分之一的患者。目前尚无针对CHIKV的循证标准治疗方法 慢性关节炎在目前的建议中，我们寻求确定复发缓解型关节炎的治疗靶点 与CHIKV感染有关。我们的受CHIKV影响的哥伦比亚患者队列（n = 500）提供了 这是进一步了解CHIKV关节炎发作免疫学的独特机会。我们的初步数据 提示调节性T细胞（Treg）功能改变可能在CHIKV关节炎发病机制中起作用。 新的低剂量白细胞介素-2（IL-2）为基础的治疗自身免疫性疾病已被证明上调 可用于CHIKV关节炎发作。我们的主要目标是进一步了解IL-2在 CHIKV关节炎中的Treg群体。我们的中心假设是慢性CHIKV关节炎活动是 与缺乏IL-2介导的Treg水平相关的低剂量IL-2是一种潜在的治疗方法。这 假设将在两个具体目标进行评估。在目标1中，我们将描述IL-2在Treg扩增中的作用。 CHIKV关节炎发作与缓解期间的相应关节炎严重程度与非关节炎相比 对照在目的2中，我们将确定IL-2疗法在小鼠CHIKV关节炎治疗中的作用。 模型这项研究的影响将确定THBE和CHIKV相关性之间的相关性。 关节痛它可以为CHIKV关节炎的低剂量IL-2治疗提供临床前评估，并深入了解 这种新的治疗方法在病毒性关节炎中的应用。

ABSTRACT Chikungunya virus (CHIKV) is an alphavirus spread by mosquitos that causes persistent arthritis in approximately one-fourth of patients. There is currently no evidence-based standard treatment for CHIKV chronic arthritis. In the current proposal, we seek to identify a therapeutic target for relapsing-remitting arthritis associated with CHIKV infection. Our Colombian cohort (n = 500) of patients affected by CHIKV affords a unique opportunity to further understand the immunology of CHIKV arthritis flares. Our preliminary data suggest that alteration of regulatory T cell (Treg) function may play a role in CHIKV arthritis pathogenesis. Novel low-dose interleukin-2 (IL-2) based therapies for autoimmune disease have been shown to up-regulate Tregs and may be of use in CHIKV arthritis flares. Our main goal is to further understand the role of IL-2 in Treg populations in CHIKV arthritis. Our central hypothesis is that chronic CHIKV arthritis activity is associated with deficient IL-2 mediated Treg levels and low-dose IL-2 is a potential therapeutic. This hypothesis will be evaluated in two specific aims. In Aim 1, we will describe the role of IL-2 in Treg expansion and corresponding arthritis severity during CHIKV arthritis flare vs. remission compared to non-arthritic controls. In Aim 2, we will determine the role of IL-2 therapy in the treatment of CHIKV arthritis in a mouse model. The impact of this research will determine the correlation between Tregs and CHIKV-associated arthralgia. It may provide a pre-clinical evaluation of low-dose IL-2 therapy for CHIKV arthritis and insights into the use of this novel therapeutic for viral arthritis in general.