German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
J Clin Invest. 2013 Feb;123(2):560-2. doi: 10.1172/JCI67548. Epub 2013 Jan 25.
The cytokine TNF-α is a major drug target for rheumatoid arthritis, an inflammatory joint disorder. An alternative approach is to target the protease TNF-α convertase (TACE), which releases TNF-α from cells. However, because TACE cleaves other proteins involved in development and cancer, a tissue-specific inhibition of TACE in immune cells appears mandatory. In this issue of the JCI, Issuree et al. report that iRHOM2 is a TACE activator in immune cells. Loss of iRHOM2 largely protects mice from inflammatory arthritis, making iRHOM2 a potential drug target for this condition.
细胞因子 TNF-α 是类风湿关节炎（一种炎症性关节疾病）的主要药物靶点。另一种方法是靶向蛋白酶 TNF-α 转化酶（TACE），它将 TNF-α 从细胞中释放出来。然而，由于 TACE 还能切割参与发育和癌症的其他蛋白，因此在免疫细胞中对 TACE 进行组织特异性抑制似乎是必需的。在本期 JCI 中，Issuree 等人报告 iRHOM2 是免疫细胞中的 TACE 激活剂。缺失 iRHOM2 可在很大程度上保护小鼠免受炎症性关节炎的侵害，这使得 iRHOM2 成为该疾病的一个潜在药物靶点。
