Abnormal intracellular distribution of NFAT1 in T lymphocytes from patients with systemic lupus erythematosus and characteristic clinical features
Abnormal intracellular distribution of NFAT1 in T lymphocytes from patients with systemic lupus erythematosus and characteristic clinical features
复制标题
DOI：
10.1016/j.clim.2006.01.001
复制
发表时间：
2006-06-01
影响因子：
8.6
通讯作者：
Tanaka, Yoshiya
中科院分区：
文献类型：
--
作者：
Fujii, Yuko;Fujii, Koichi;Tanaka, Yoshiya
系统性红斑狼疮（SLE）的临床表现多种多样，但其发病机制尚不清楚。在SLE的免疫中，受损的T细胞受体（TCR）信号传导和改变的细胞因子产生是发病机制的中心，尽管对狼疮T淋巴细胞中的NFAT（活化T细胞的核因子）知之甚少。TCR刺激通过Ca 2 + /钙调神经磷酸酶（Cn）途径激活NFAT 1，促进NFAT 1从胞质溶胶的核转位。因此，我们研究了疾病的活动/功能和细胞内NFAT 1定位在T淋巴细胞从活动性狼疮患者的分馏的关系。结果表明，疾病活动和NFAT 1分布之间没有显着的关系。然而，有趣的是，我们在活动性狼疮肾炎或胸膜炎患者的颗粒中观察到NFAT 1的偏态分布。体外环孢素A治疗提示狼疮T淋巴细胞自主激活C2+/Cn通路。考虑到这些结果，NFAT 1可能在SLE中呈现临床异质性。(c)2006年爱思唯尔公司All rights reserved.
Systemic lupus erythematosus (SLE) presents various clinical features; however, underlying mechanisms remain unclear. In the immunity of SLE, impaired T cell receptor (TCR) signaling and altered cytokine production are in the center of pathogenesis, although, little is known about NFAT (nuclear factor of activated T cells) in lupus T lymphocytes. TCR stimulation activates NFAT1 through Ca2+ /calcineurin (Cn) pathway, facilitating nuclear translocation of NFAT1 from cytosol. Therefore, we investigated relationship of disease activity/features and intracellular NFAT1 localization in T lymphocytes from active lupus patients by fractionation. Results showed no significant relationship between disease activity and NFAT1 distribution. However, interestingly, we observed skewed NFAT1 distribution in pellet in patients with active lupus nephritis or pleuritis. In vitro cyclosporin A treatment suggested autonomously activated C2+/Cn pathway in lupus T lymphocytes. Considering these results, NFAT1 might be presenting the clinical heterogeneity in SLE. (c) 2006 Elsevier Inc. All rights reserved.