Signal transducer and activator of transcription (STAT) 3 inhibition delays the onset of lupus nephritis in MRL/lpr mice.
Signal transducer and activator of transcription (STAT) 3 inhibition delays the onset of lupus nephritis in MRL/lpr mice.
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DOI：
10.1016/j.clim.2015.04.004
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发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Kyttaris V
中科院分区：
文献类型：
--
作者：
Edwards LJ;Mizui M;Kyttaris V
转录因子STAT3在SLE患者的T细胞中过表达和过度活化。STAT3在T细胞分化为Th17和T滤泡辅助细胞中起核心作用，Th17和T滤泡辅助细胞是SLE中协调自身免疫应答的两个亚群。此外，STAT3在趋化因子介导的T细胞迁移中是重要的。为了更好地了解其在SLE中的作用，我们使用小分子Stattic抑制狼疮易感小鼠中的STAT3。Stattic治疗的小鼠表现出延迟的蛋白尿发作（比对照组晚3周），并且具有较低水平的抗dsDNA抗体和炎性细胞因子。抑制剂治疗减少淋巴结病，导致总T细胞数量减少3倍，T滤泡辅助细胞数量减少4倍。体外实验表明，Stattic处理的T细胞表现出增殖降低和迁移至CXCL12的能力降低。我们认为STAT3抑制是SLE，特别是狼疮性肾炎的治疗靶点。
The transcription factor STAT3 is overexpressed and hyperactivated in T cells from SLE patients. STAT3 plays a central role in T cell differentiation into Th17 and T follicular helper cells, two subsets that orchestrate autoimmune responses in SLE. Moreover, STAT3 is important in chemokine-mediated T cell migration. To better understand its role in SLE, we inhibited STAT3 in lupus-prone mice using the small molecule Stattic. Stattic-treated mice exhibited delayed onset of proteinuria (3 weeks later than controls), and had lower levels of anti-dsDNA antibodies and inflammatory cytokines. Inhibitor treatment reduced lymphadenopathy, resulted in a 3-fold decrease in total T cell number, and a 4-fold decrease in the numbers of T follicular helper cells. In vitro experiments showed that Stattic-treated T cells exhibited decreased proliferation and a decrease in ability to migrate to CXCL12. We propose that STAT3 inhibition represents a therapeutic target in SLE, particularly lupus nephritis.
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影响因子：
32.4
作者：
Nurieva, Roza I.;Chung, Yeonseok;Hwang, Daehee;Yang, Xuexian O.;Kang, Hong Soon;Ma, Li;Wang, Yi-Hong;Watowich, Stephanie S.;Jetten, Anton M.;Tian, Qiang;Dong, Chen
通讯作者：
Dong, Chen
DOI：
10.1073/pnas.94.5.1925
发表时间：
1997-03-04
影响因子：
11.1
作者：
Bleul, CC;Wu, LJ;Mackay, CR
通讯作者：
Mackay, CR
DOI：
10.1016/j.clim.2012.09.009
发表时间：
2013-09
期刊：
Clinical immunology (Orlando, Fla.)
影响因子：
--
作者：
Markopoulou A;Kyttaris VC
通讯作者：
Kyttaris VC
DOI：
10.4049/jimmunol.0801920
发表时间：
2009-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Wang A;Fairhurst AM;Tus K;Subramanian S;Liu Y;Lin F;Igarashi P;Zhou XJ;Batteux F;Wong D;Wakeland EK;Mohan C
通讯作者：
Mohan C
全身性红斑狼疮中T细胞的病理。
影响因子：
4.1
作者：
Mak A;Kow NY
通讯作者：
Kow NY