Systems biology of lupus: mapping the impact of genomic and environmental factors on gene expression signatures, cellular signaling, metabolic pathways, hormonal and cytokine imbalance, and selecting targets for treatment.
Systems biology of lupus: mapping the impact of genomic and environmental factors on gene expression signatures, cellular signaling, metabolic pathways, hormonal and cytokine imbalance, and selecting targets for treatment.
复制标题
DOI：
10.3109/08916930903374774
复制
发表时间：
2010-02
期刊：
影响因子：
3.5
通讯作者：
Perl A
中科院分区：
文献类型：
--
作者：
Perl A
系统性红斑狼疮（SLE）的特征在于T细胞、B细胞和树突状细胞的功能障碍，促炎性核物质从坏死细胞中释放，以及抗核抗体（ANA）和ANA与DNA、RNA和核蛋白的免疫复合物的形成。雷帕霉素哺乳动物靶蛋白（mTOR）的激活最近已成为SLE中T细胞和B细胞异常激活的关键因素。在T细胞中，一氧化氮和线粒体超极化（MHP）的产生增加被确定为mTOR激活上游的代谢检查点。mTOR通过增加核内体再循环调节因子Rab 5和HRES-1/Rab 4基因的表达来控制T细胞受体相关信号蛋白CD 4和CD 3 γ的表达，增强T和B细胞中的Ca 2+流动并使酪氨酸激酶的表达偏斜，并阻断Foxp 3的表达和调节性T细胞的产生。MHP、mTOR、Ra B GTP酶和Syk激酶活性增加以及Ca 2+通量增加已成为SLE中常见的T和B细胞生物标志物和治疗靶点。
Systemic lupus erythematosus (SLE) is characterized by the dysfunction of T cells, B cells, and dendritic cells, the release of pro-inflammatory nuclear materials from necrotic cells, and the formation of antinuclear antibodies (ANA) and immune complexes of ANA with DNA, RNA, and nuclear proteins. Activation of the mammalian target of rapamycin (mTOR) has recently emerged as a key factor in abnormal activation of Tand B cells in SLE. In T cells, increased production of nitric oxide and mitochondrial hyperpolarization (MHP) were identified as metabolic checkpoints upstream of mTOR activation. mTOR controls the expression T-cell receptor-associated signaling proteins CD4 and CD3ζ through increased expression of the endosome recycling regulator Rab5 and HRES-1/Rab4 genes, enhances Ca2+ fluxing and skews the expression of tyrosine kinases both in T and B cells, and blocks the expression of Foxp3 and the generation of regulatory T cells. MHP, increased activity of mTOR, Rab GTPases, and Syk kinases, and enhanced Ca2+ flux have emerged as common Tand B cell biomarkers and targets for treatment in SLE.
登录
查看更多内容
影响因子：
13.6
作者：
Crispin, Jose C.;Alcocer-Varela, Jorge
通讯作者：
Alcocer-Varela, Jorge
影响因子：
4.8
作者：
Banki, K;Hutter, E;Perl, A
通讯作者：
Perl, A
影响因子：
158.5
作者：
Arbuckle, MR;McClain, MT;Harley, JB
通讯作者：
Harley, JB
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V
影响因子：
15.9
作者：
Cappione, A;Anolik, JH;Sanz, I
通讯作者：
Sanz, I