Myeloid-Derived Suppressor Cells Induce Podocyte Injury Through Increasing Reactive Oxygen Species in Lupus Nephritis.
Myeloid-Derived Suppressor Cells Induce Podocyte Injury Through Increasing Reactive Oxygen Species in Lupus Nephritis.
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狼疮性肾炎中髓源性抑制细胞通过增加活性氧诱导足细胞损伤
DOI：
10.3389/fimmu.2018.01443
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发表时间：
2018
影响因子：
7.3
通讯作者：
Hou Y
中科院分区：
文献类型：
--
作者：
Zhang D;Xu J;Ren J;Ding L;Shi G;Li D;Dou H;Hou Y
髓源性抑制细胞（MDSC）的扩增已在小鼠模型和狼疮性肾炎（LN）患者中得到证实，但MDSC在此过程中的确切作用在很大程度上仍然未知。在这项研究中，我们调查是否MDSCs参与足细胞损伤的过程中LN的发展。在Toll样受体-7（TLR-7）激动剂咪喹莫特诱导的狼疮小鼠中，我们发现狼疮小鼠肾小球足细胞严重损伤，脾和肾中MDSCs显著扩增。TLR-7激活的MDSCs在体内外活性氧（ROS）的产生增加，其功能增强。MDSCs产生的ROS通过激活p38 MAPK和NF-kB信号通路诱导足细胞损伤。此外，我们证实足细胞损伤确实与降植烷诱导的狼疮小鼠LN中MDSC的扩增及其ROS分泌相关。这些结果首次表明LN足细胞损伤与肾脏MDSC的增加有关，MDSC可能是未来LN治疗的一个有希望的靶点。
The expansion of myeloid-derived suppressor cells (MDSCs) has been documented in murine models and patients with lupus nephritis (LN), but the exact role of MDSCs in this process remains largely unknown. In this study, we investigated whether MDSCs are involved in the process of podocyte injury in the development of LN. In toll-like receptor-7 (TLR-7) agonist imiquimod-induced lupus mice, we found the severe podocyte injury in glomeruli of lupus mice and significant expansion of MDSCs in spleens and kidneys of lupus mice. The function of TLR-7 activated MDSCs was enhanced including the increased generation of reactive oxygen species (ROS) in vivo and in vitro. Moreover, the ROS production of MDSCs induced podocyte injury through activating the p-38MAPK and NF-kB signaling. Furthermore, we verified that podocyte injury was indeed correlated with expansion of MDSCs and their ROS secretion in LN of pristane-induced lupus mice. These findings first indicate that the podocyte injury in LN was associated with the increased MDSCs in kidney and MDSCs may be a promising therapeutic target of LN in the future.
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影响因子：
13.3
作者：
Lourenco, Elaine V.;Wong, Maida;Skaggs, Brian J.
通讯作者：
Skaggs, Brian J.
DOI：
10.4049/jimmunol.1401720
发表时间：
2014-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Soni C;Wong EB;Domeier PP;Khan TN;Satoh T;Akira S;Rahman ZS
通讯作者：
Rahman ZS
影响因子：
11.2
作者：
Chen S;Wang L;Fan J;Ye C;Dominguez D;Zhang Y;Curiel TJ;Fang D;Kuzel TM;Zhang B
通讯作者：
Zhang B
DOI：
10.1152/ajprenal.00111.2015
发表时间：
2015-11-01
影响因子：
4.2
作者：
Sverrisson, Kristinn;Axelsson, Josefin;Rippe, Bengt
通讯作者：
Rippe, Bengt
影响因子：
13.6
作者：
Banas, Miriam C.;Banas, Bernhard;Alpers, Charles E.
通讯作者：
Alpers, Charles E.