Malemud Charles J
Department of Medicine, Division of Rheumatic Diseases, Case Western Reserve University School of Medicine, Foley Medical Building, 2061 Cornell Road, Suite 207, Cleveland, OH 44122-5076, USA.
Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
Cells. 2018 Nov 22;7(12):223. doi: 10.3390/cells7120223.
Rheumatoid arthritis (RA) is a chronic, progressive, systemic autoimmune disease that mostly affects small and large synovial joints. At the molecular level, RA is characterized by a profoundly defective innate and adaptive immune response that results in a chronic state of inflammation. Two of the most significant alterations in T-lymphocyte (T-cell) dysfunction in RA is the perpetual activation of T-cells that result in an abnormal proliferation state which also stimulate the proliferation of fibroblasts within the joint synovial tissue. This event results in what we have termed "apoptosis resistance", which we believe is the leading cause of aberrant cell survival in RA. Finding therapies that will induce apoptosis under these conditions is one of the current goals of drug discovery. Over the past several years, a number of T-cell subsets have been identified. One of these T-cell subsets are the T-regulatory (T) cells. Under normal conditions T cells dictate the state of immune tolerance. However, in RA, the function of T cells become compromised resulting in T cell dysfunction. It has now been shown that several of the drugs employed in the medical therapy of RA can partially restore T cell function, which has also been associated with amelioration of the clinical symptoms of RA.
类风湿性关节炎（RA）是一种慢性、进行性、全身性自身免疫性疾病，主要影响大小滑膜关节。在分子水平上，RA的特征是先天性和适应性免疫反应存在严重缺陷，导致慢性炎症状态。RA中T淋巴细胞（T细胞）功能障碍的两个最显著改变是T细胞的持续激活，这导致异常增殖状态，同时也刺激关节滑膜组织中成纤维细胞的增殖。这一事件导致了我们所说的“抗凋亡”，我们认为这是RA中异常细胞存活的主要原因。找到在这些条件下诱导细胞凋亡的疗法是当前药物研发的目标之一。在过去几年中，已经鉴定出许多T细胞亚群。其中一个T细胞亚群是调节性T（Treg）细胞。在正常情况下，Treg细胞决定免疫耐受状态。然而，在RA中，Treg细胞的功能受损，导致T细胞功能障碍。现已表明，RA医学治疗中使用的几种药物可以部分恢复T细胞功能，这也与RA临床症状的改善有关。
