Phosphorylated ERM is responsible for increased T cell polarization, adhesion, and migration in patients with systemic lupus erythematosus
Phosphorylated ERM is responsible for increased T cell polarization, adhesion, and migration in patients with systemic lupus erythematosus
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DOI：
10.4049/jimmunol.178.3.1938
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发表时间：
2007-02-01
影响因子：
4.4
通讯作者：
Tsokos, George C.
中科院分区：
文献类型：
--
作者：
Li, Yansong;Harada, Tatsuhiro;Tsokos, George C.
系统性红斑狼疮（SLE）是一种自身免疫/炎症性疾病，其特征是自身抗体产生以及通过尚不明确的机制浸润组织的异常T细胞。我们报道，与类风湿关节炎患者和正常人的T细胞相比，SLE的T淋巴细胞表现出CD44、埃兹蛋白、根蛋白和膜突蛋白（ERM）磷酸化水平升高、肌动蛋白聚合作用更强、极性帽形成更明显以及黏附和趋化迁移能力增强。在SLE的T细胞中，通过CD44小干扰RNA沉默CD44，可显著抑制其黏附和迁移能力，使用Rho激酶和肌动蛋白聚合抑制剂进行治疗也有同样效果。强制表达磷酸化模拟形式的T567D - 埃兹蛋白，可显著提高正常T细胞的黏附和迁移速率。SLE血清中存在的抗CD3/TCR自身抗体可导致正常T细胞的ERM磷酸化、黏附和迁移增加。在狼疮性肾炎患者肾脏浸润的T细胞中，磷酸化的ERM（pERM）和CD44高表达。这些数据证明，ERM磷酸化增加是引导SLE患者T细胞黏附和迁移的关键分子异常。
Systemic lupus erythematosus (SLE) is an autoimmune/inflammatory disease characterized by autoantibody production and abnormal T cells that infiltrate tissues through not well-known mechanisms. We report that SLE T lymphocytes display increased levels of CD44, ezrin, radixin, and moesin (ERM) phosphorylation, stronger actin polymerization, higher polar cap formation, and enhanced adhesion and chemotactic migration compared with T cells from patients with rheumatoid arthritis and normal individuals. Silencing of CD44 by CD44 small interfering RNA in SLE T cells inhibited significantly their ability to adhere and migrate as did treatment with Rho kinase and actin polymerization inhibitors. Forced expression of T567D-ezrin, a phosphorylation-mimic form, enhanced remarkably the adhesion and migration rate of normal T cells. Anti-CD3/TCR autoantibodies present in SLE sera caused increased ERM phosphorylation, adhesion, and migration in normal T cells. pERM and CD44 are highly expressed in T cells infiltrating in the kidneys of patients with lupus nephritis. These data prove that increased ERM phosphorylation represents a key molecular abnormality that guides T cell adhesion and migration in SLE patients.