The role of SOCS-1 and SOCS-3 in regulating acute inflammatory arthritis.

类风湿性关节炎（RA）是一种以关节为主要靶点的慢性炎症性疾病。该疾病导致慢性关节疼痛、僵硬和关节活动能力丧失，导致日常活动越来越困难。类风湿性关节炎的治疗已逐渐改善，但对许多患者来说仍然不够。虽然原因尚不清楚，但在了解驱动RA的分子途径方面取得了进展。这种疾病的特点是产生高水平的炎症介质，称为细胞因子。这一发现导致了特异性细胞因子抑制剂的发展和引入临床实践，尽管相当多的患者对治疗没有反应。开发风湿性关节炎新疗法的另一种方法是使用人体的天然抑制剂来限制炎症细胞因子的作用。其中一种抑制剂是细胞因子信号传导抑制因子1 （SOCS-1）。通过动物模型，我们发现缺乏SOCS-1的小鼠会患上更严重的关节炎，并确定了它作用的不同细胞类型。在SOCS-1可以作为RA的治疗方法之前，还需要进一步的研究。我们的目标是确定当SOCS-1缺失时导致疾病严重程度增加的主要细胞类型。这将使治疗能够针对关节中最合适的细胞。我们还打算研究相关分子SOCS-3，看看它是否有类似的抑制疾病严重程度的作用。这些研究将提供更多关于炎性疾病特别是类风湿性关节炎中SOCS蛋白活性的信息，并可能导致治疗类风湿性关节炎的新方法。

Rheumatoid arthritis (RA) is a chronic inflammatory disease which mainly targets joints. The disease causes chronic joint pain, stiffness and loss of joint mobility, leading to increasing difficulty in carrying out day to day activities. Treatment for RA has gradually improved, but remains inadequate for many patients. Although the cause is unknown, progress has been made in understanding the molecular pathways which drive RA. The disease is characterised by the production of high levels of inflammatory mediators called cytokines. This finding has led to the development and introduction of specific cytokine inhibitors into clinical practice, although a significant number of patients fail to respond to treatment. An alternative approach to develop new treatments for RA would be to use the body's natural inhibitors to limit the actions of inflammatory cytokines. One such inhibitor is Suppressor of Cytokine Signalling-1 (SOCS-1). Using animal models, we have shown that mice lacking SOCS-1 develop more severe arthritis and have identified the different cell types it acts on. Further studies are still needed before SOCS-1 can be developed as a treatment for RA. We aim to identify the major cell type responsible for the increased severity of disease seen when SOCS-1 is absent. This will allow for treatment to be targetted to the most appropriate cells in the joint. We also aim to study the related molecule SOCS-3, to see whether it has similar effects on inhibiting the severity of disease. These studies will provide more information on the activity of SOCS proteins during inflammatory diseases in general and RA in particular and and may lead to new approaches for the treatment of RA.