CXCL16/CXCR6 and Their Roles in Autoimmune Arthritis

类风湿性关节炎(RA)的病因和发病机制仍不清楚 调查。趋化因子在吸引和保留炎症关节中的白细胞方面起着关键作用。 然而，细胞在关节中定位的确切机制尚不清楚。 这个项目的长期目标是了解细胞转运和炎症的机制。 自身免疫性疾病背景下非淋巴组织的反应。最近我们发现， 新发现的趋化因子CXCL16及其受体CXCR6在小鼠关节中高表达 胶原诱导性关节炎(CIA)，类风湿关节炎的动物模型。CXCL16是委员会的第二个成员 具有跨膜结构域的趋化因子家族。显示，携带受体的细胞主要是Th1细胞 淋巴外组织的归巢潜能，并在类风湿关节炎患者的炎症滑液中丰富。治疗 携带CXCL16-LG融合蛋白的小鼠可显著改善CIA。因此，我们假设 CXCL16/CXCR6在自身免疫性关节炎的发病机制中起重要作用。这个项目将专注于 CXCL16/CXCR6的表达调控机制及其在细胞周期调控中的作用 中央情报局的成立和发展。Th1介导的趋化因子优先表达 像RA这样的炎症性疾病，如CXCR3和CCR5，也将在 以进一步阐明CXCL16/CXCR6在CIA发病机制中的作用。在……里面 此外，我们假设CXCL16/CXCR6可能介导T细胞、B细胞、 巨噬细胞和其他细胞因其独特的结构CXCL16而在受影响的部位形成膜 趋化因子及其表达模式。CXCL16/CXCR6在介导T细胞抗原提呈中的作用 将对细胞进行研究。除了加强我们对类风湿关节中白细胞迁移的理解外， 这些研究有望为趋化因子在调控中的作用提供重要信息 炎症反应中淋巴细胞和巨噬细胞的激活和分化。这项研究 还将为设计抗炎药治疗自身免疫性关节炎和 其他自身免疫性疾病。

The etiology and pathogenesis of rheumatoid arthritis (RA) remain obscure despite intense investigation. Chemokines play a critical role in attracting and retaining leukocytes in the inflamed joints. However, the precise mechanism for cell positioning in the joints is unclear. The long-term goal of this project is to understand the mechanism of cell trafficking and inflammatory responses in nonlymphoid tissues in the settings of autoimmune diseases. Recently we have found that CXCL16, a newly identified chemokine, and its receptor, CXCR6, are highly expressed in the joints of mice with collagen-induced arthritis (CIA), an animal model of RA. CXCL16 is the second member of the chemokine family with a transmembrane domain. The receptor-bearing cells are mainly Th1 cells, display extralymphoid tissue homing potential and are enriched in inflamed synovial fluid of RA patients. Treatment of mice with CXCL16-lg fusion protein significantly ameliorates CIA. Thus, we hypothesize that CXCL16/CXCR6 play an important role in the pathogenesis of autoimmune arthritis. This project will focus on the mechanisms that regulate CXCL16/CXCR6 expression and the contribution of CXCL16/CXCR6 to the initiation and progression of CIA. Chemokines that are preferentially expressed in Th1-mediated inflammatory disorders like RA, such as CXCR3 and CCR5, will also be investigated during the course of CIA as comparative studies to further elucidate the role of CXCL16/CXCR6 in the pathogenesis of CIA. In addition, we hypothesize that CXCL16/CXCR6 may mediate interactions among T cell, B cells, macrophages and other cells in the affected sites because of the unique structure CXCL16 as a membrane chemokine and its expression pattern. The role of CXCL16/CXCR6 in mediating T cell-antigen presenting cells will be studied. Aside from enhancing our understanding of leukocyte migration in rheumatoid joints, these studies are expected to provide important information regarding chemokine functions in regulating activation and differentiation of lymphocytes and macrophages during inflammatory responses. The study will also provide insights into new targets for designing anti-inflammatory agents in autoimmune arthritis and other autoimmune diseases.