Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival.
Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival.
复制标题
DOI：
10.1002/emmm.201201544
复制
发表时间：
2013-01
影响因子：
11.1
通讯作者：
Appel, Stanley H.
中科院分区：
文献类型：
--
作者：
Henkel, Jenny S.;Beers, David R.;Wen, Shixiang;Rivera, Andreana L.;Toennis, Karen M.;Appel, Joan E.;Zhao, Weihua;Moore, Dan H.;Powell, Suzanne Z.;Appel, Stanley H.
在肌萎缩性侧索硬化症（ALS）小鼠中，调节性t淋巴细胞（Tregs）具有神经保护作用，可减缓疾病进展。为了确定Treg和FoxP3 （Treg功能所需的转录因子）是否类似地影响ALS患者的进展率，我们用流式细胞术评估了患者的t淋巴细胞。在快速进展的ALS患者中，treg数量及其FoxP3蛋白表达均降低，且与进展率呈负相关。FoxP3、TGF-β、IL4和Th2转录因子Gata3的mRNA水平在快速进展的患者中降低，并与进展率呈负相关。FoxP3和Gata3都是进展率的准确指标。在进展缓慢和快速的患者中，IL10、Tbx21、Th1转录因子或IFN-γ的表达没有差异。一项为期3.5年的前瞻性研究显示，早期FoxP3水平的降低表明了收集时的进展率，并预测了未来的快速进展和降低的生存期。总的来说，这些数据表明Tregs和Th2淋巴细胞影响疾病进展率。重要的是，早期FoxP3水平降低可用于识别快速进展的患者。
In amyotrophic lateral sclerosis (ALS) mice, regulatory T-lymphocytes (Tregs) are neuroprotective, slowing disease progression. To address whether Tregs and FoxP3, a transcription factor required for Treg function, similarly influence progression rates of ALS patients, T-lymphocytes from patients were assessed by flow cytometry. Both numbers of Tregs and their FoxP3 protein expressions were reduced in rapidly progressing ALS patients and inversely correlated with progression rates. The mRNA levels of FoxP3, TGF-β, IL4 and Gata3, a Th2 transcription factor, were reduced in rapidly progressing patients and inversely correlated with progression rates. Both FoxP3 and Gata3 were accurate indicators of progression rates. No differences in IL10, Tbx21, a Th1 transcription factor or IFN-γ expression were found between slow and rapidly progressing patients. A 3.5-year prospective study with a second larger cohort revealed that early reduced FoxP3 levels were indicative of progression rates at collection and predictive of future rapid progression and attenuated survival. Collectively, these data suggest that Tregs and Th2 lymphocytes influence disease progression rates. Importantly, early reduced FoxP3 levels could be used to identify rapidly progressing patients.
登录
查看更多内容
DOI：
10.1093/brain/awr074
发表时间：
2011-05
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Beers DR;Henkel JS;Zhao W;Wang J;Huang A;Wen S;Liao B;Appel SH
通讯作者：
Appel SH
影响因子：
11.2
作者：
Henkel, JS;Engelhardt, JI;Appel, SH
通讯作者：
Appel, SH
影响因子：
14.5
作者：
HAVERKAMP, LJ;APPEL, V;APPEL, SH
通讯作者：
APPEL, SH
DOI：
10.4049/jimmunol.0803982
发表时间：
2009-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Reynolds AD;Stone DK;Mosley RL;Gendelman HE
通讯作者：
Gendelman HE
影响因子：
3.3
作者：
Mantovani, Stefania;Garbelli, Silvia;Mora, Gabriele
通讯作者：
Mora, Gabriele