Regulation and function of CCR2 on T cells in Rheumatoid Arthritis

摘要 类风湿关节炎(RA)是一种以慢性炎症为特征的全身性自身免疫性疾病。 滑膜和单个核细胞向关节内渗透。一旦进入关节，单个核细胞， 主要是T细胞和巨噬细胞，对疾病的病理有重大贡献，但其机制是通过 这些细胞进入关节的原因尚不清楚。为了回答这个问题，我们决定调查 趋化因子受体在浸润性T细胞上的表达趋化因子受体是一种跨膜蛋白 促进免疫细胞向各自细胞因子梯度迁移的受体。以前的工作在 实验室发现，炎症的滑膜中有大量T细胞表达趋化因子受体CCR2。在……里面 此外，来自其他研究小组的研究一直表明，CCR2在RA患者中的表达升高 然而，血液中还没有关于类风湿关节炎患者T细胞特异性CCR2丢失的研究。另外， 趋化因子受体常被用作识别辅助T细胞功能亚群的标志物。考虑到 在炎症的滑膜中有大量表达CCR2的T细胞，我们推测CCR2可能 促进炎症滑膜内的迁移或定位，并可能划分功能T细胞 人口。此外，对CCR2在T细胞上的表达调节知之甚少 对其规定的了解可使拟议的迁移性或功能性方案得以调整。 因此，我们建议对CCR2在T细胞中的调节和功能进行强有力的研究 细胞学、转录学、功能性和小鼠系统，以彻底表征这一群体，并更好地 了解其在类风湿关节炎发病机制中的作用。

Abstract Rheumatoid Arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the synovium and infiltration of mononuclear cells into the joint. Once in the joint the mononuclear cells, predominantly T cells and macrophages, contribute significantly to disease pathology, yet the mechanism by which these cells enter the joint is not clearly established. To answer this question, we decided to investigate the expression of chemokine receptors on infiltrating T cells. Chemokine receptors are transmembrane protein receptors that facilitate immune cell migration towards gradients of their respective cytokines. Previous work in the lab found a large population of T cells in the inflamed synovium express the chemokine receptor CCR2. In addition, work from other groups have consistently shown an elevated expression of CCR2 in RA patient blood, however, there have not been investigations into T cell specific loss of CCR2 in RA. Additionally, chemokine receptors are often used as markers to identify functional subsets of helper T cells. Considering the robust population of T cells expressing CCR2 in the inflamed synovium, we hypothesized that CCR2 may facilitate migration or positioning within the inflamed synovium and may demarcate a functional T cell population. Furthermore, very little is known about the regulation of CCR2 expression on T cells and better understanding of its regulation could allow for modulation of the proposed migratory or functional programming. Therefore, we are proposing a robust investigation into the regulation and function of CCR2 in T cells utilizing cytometric, transcriptomic, functional, and murine systems to thoroughly characterize this population and better understand its role in RA pathogenesis.