Calcium signaling in systemic lupus erythematosus T cells: a treatment target.
Calcium signaling in systemic lupus erythematosus T cells: a treatment target.
复制标题
DOI：
10.1002/art.30353
复制
发表时间：
2011-07
影响因子：
--
通讯作者：
Tsokos, George C.
中科院分区：
文献类型：
--
作者：
Kyttaris, Vasileios C.;Zhang, Zheng;Kampagianni, Ourania;Tsokos, George C.
系统性红斑狼疮(SLE)T细胞表现为钙调神经磷酸酶-NFAT途径的高活性。本研究的目的是回答这一途径是否与SLE T细胞功能异常有关，并测试新近发现的钙调神经磷酸酶抑制剂潘生丁在限制SLE相关病理方面的有效性。从SLE患者和正常人外周血中分离T细胞和单个核细胞。从狼疮易感MRL/LPR小鼠和对照MRL/MPJ小鼠的脾和淋巴结中分离出小鼠细胞。在体外用他克莫司、潘生丁或对照组处理细胞。MRL/lpr小鼠每周3次腹腔注射双嘧达莫50 mg/kg，共3周。MRL/LPR T细胞，尤其是CD3+CD4-CD8-在激活和NFATc1水平增加时显示出强劲的钙内流。MRL/LPR T细胞(包括CD4+和CD3+CD4-CD8-细胞)帮助B细胞以钙调神经磷酸酶依赖的方式产生免疫球蛋白。潘生丁可显著抑制T细胞CD15 4的表达、干扰素-γ、IL-17、IL-6的产生以及T细胞依赖性B细胞免疫球蛋白的分泌。双嘧达莫治疗MRL/LPR小鼠可减轻狼疮性肾炎，防止皮肤溃疡的出现。NFAT活化是SLE T细胞活化和产生免疫球蛋白的关键步骤。潘生丁抑制狼疮小鼠的SLE T细胞功能，改善疾病病理。我们建议双嘧达莫可用于SLE患者的治疗方案。
Systemic lupus erythematosus (SLE) T cells display a hyperactive calcineurin-NFAT pathway. The aim of this study is to answer whether this pathway is responsible for the aberrant SLE T cell function and test the effectiveness of the recently recognized calcineurin inhibitor dipyridamole in limiting SLE related pathology. T and mononuclear cells were isolated from the peripheral blood of patients with SLE and healthy individuals. Murine cells were isolated from the spleens and lymph nodes of lupus prone MRL/lpr mice and control MRL/MpJ mice. Cells were treated in vitro with tacrolimus, dipyridamole or control. MRL/lpr mice were injected intraperitoneally with dipyridamole 50 mg/kg three times a week for 3 weeks. MRL/lpr T cells, especially CD3+CD4-CD8- displayed a robust calcium influx upon activation and increased levels of NFATc1. MRL/lpr T cells (both CD4+ and CD3+CD4-CD8- cells) provided help to B cells to produce immunoglobulin in a calcineurin-dependent fashion. Dipyridamole treatment of SLE T cells inhibited significantly the expression of CD154, the production of IFN-γ, IL-17, IL-6, and the T cell dependent B cell immunoglobulin secretion. Treatment of MRL/lpr mice with dipyridamole alleviated lupus nephritis and prevented the appearance of skin ulcers. NFAT activation is a key step in the activation of SLE T cells and the production of immunoglobulin. Dipyridamole inhibits SLE T cell function and improves disease pathology in lupus-prone mice. We propose that dipyridamole can be used in treatment regimens of SLE patients.
登录
查看更多内容
影响因子：
13.6
作者：
Crispín JC;Liossis SN;Kis-Toth K;Lieberman LA;Kyttaris VC;Juang YT;Tsokos GC
通讯作者：
Tsokos GC
影响因子：
4.4
作者：
Krishnan, S;Nambiar, MP;Tsokos, GC
通讯作者：
Tsokos, GC
DOI：
10.4049/jimmunol.0900385
发表时间：
2009-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Zhang Z;Kyttaris VC;Tsokos GC
通讯作者：
Tsokos GC
霍乱毒素B通过促进脂质筏聚集来加速狼疮易发的疾病进展。
DOI：
10.4049/jimmunol.181.6.4019
发表时间：
2008-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Deng GM;Tsokos GC
通讯作者：
Tsokos GC
DOI：
10.4049/jimmunol.0903595
发表时间：
2010-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kyttaris VC;Zhang Z;Kuchroo VK;Oukka M;Tsokos GC
通讯作者：
Tsokos GC