γδT Cells Exacerbate Podocyte Injury via the CD28/B7-1-Phosphor-SRC Kinase Pathway.
γδT Cells Exacerbate Podocyte Injury via the CD28/B7-1-Phosphor-SRC Kinase Pathway.
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DOI：
10.1155/2018/5647120
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发表时间：
2018
影响因子：
--
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Chen W;Wu Y;Zhang G;Wang M;Yang H;Li Q
Primary nephrotic syndrome (PNS) is a devastating pediatric disorder. However, its mechanism remains unclear. Previous studies detected B7-1 in podocytes; meanwhile, γδT cells play pivotal roles in immune diseases. Therefore, this study aimed to assess whether and how γδT cells impact podocytes via the CD28/B7-1 pathway. WT and TCRδ−/− mice were assessed. LPS was used to induce nephropathy. Total γδT and CD28+γδT cells were quantitated in mouse spleen and kidney samples. B7-1 and phosphor-SRC levels in the kidney were detected as well. In vitro, γδT cells from the mouse spleen were cocultured with mouse podocytes, and apoptosis rate and phosphor-SRC expression in podocytes were assessed. Compared with control mice, WT mice with LPS nephropathy showed increased amounts of γδT cells in the kidney. Kidney injury was alleviated in TCRδ−/− mice. Meanwhile, B7-1 and phosphor-SRC levels were increased in the kidney from WT mice with LPS nephropathy. CD28+γδT cells were decreased, indicating CD28 may play a role in LPS nephropathy. Immunofluorescence colocalization analysis revealed a tight association of γδT cells with B7-1 in the kidney. High B7-1 expression was detected in podocytes treated with LPS. Podocytes cocultured with γδT cells showed higher phosphor-SRC and apoptosis rate than other cell groups. Furthermore, CD28/B7-1 blockage with CTLA4-Ig in vitro relieved podocyte injury. γδT cells exacerbate podocyte injury via CD28/B7-1 signaling, with downstream involvement of phosphor-SRC. The CD28/B7-1 blocker CTLA4-Ig prevented progressive podocyte injury, providing a potential therapeutic tool for PNS.
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影响因子：
3.7
作者：
Bertelli R;Di Donato A;Cioni M;Grassi F;Ikehata M;Bonanni A;Rastaldi MP;Ghiggeri GM
通讯作者：
Ghiggeri GM
肾小球足细胞的先天免疫活性
影响因子：
7.3
作者：
Xia H;Bao W;Shi S
通讯作者：
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影响因子：
16.6
作者：
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通讯作者：
Iwakura Y
DOI：
10.1056/nejmoa1304572
发表时间：
2013-12-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Yu CC;Fornoni A;Weins A;Hakroush S;Maiguel D;Sageshima J;Chen L;Ciancio G;Faridi MH;Behr D;Campbell KN;Chang JM;Chen HC;Oh J;Faul C;Arnaout MA;Fiorina P;Gupta V;Greka A;Burke GW 3rd;Mundel P
通讯作者：
Mundel P
DOI：
10.1073/pnas.91.20.9347
发表时间：
1994-09-27
影响因子：
11.1
作者：
AUGUST, A;GIBSON, S;DUPONT, B
通讯作者：
DUPONT, B