| First Author | Chen W | Year | 2018 |
| Journal | Biomed Res Int | Volume | 2018 |
| Pages | 5647120 | PubMed ID | 29862277 |
| Mgi Jnum | J:277516 | Mgi Id | MGI:6296317 |
| Doi | 10.1155/2018/5647120 | Citation | Chen W, et al. (2018) gammadeltaT Cells Exacerbate Podocyte Injury via the CD28/B7-1-Phosphor-SRC Kinase Pathway. Biomed Res Int 2018:5647120 |
| abstractText | Primary nephrotic syndrome (PNS) is a devastating pediatric disorder. However, its mechanism remains unclear. Previous studies detected B7-1 in podocytes; meanwhile, gammadeltaT cells play pivotal roles in immune diseases. Therefore, this study aimed to assess whether and how gammadeltaT cells impact podocytes via the CD28/B7-1 pathway. WT and TCRdelta(-/-) mice were assessed. LPS was used to induce nephropathy. Total gammadeltaT and CD28(+)gammadeltaT cells were quantitated in mouse spleen and kidney samples. B7-1 and phosphor-SRC levels in the kidney were detected as well. In vitro, gammadeltaT 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 gammadeltaT cells in the kidney. Kidney injury was alleviated in TCRdelta(-/-) mice. Meanwhile, B7-1 and phosphor-SRC levels were increased in the kidney from WT mice with LPS nephropathy. CD28(+)gammadeltaT cells were decreased, indicating CD28 may play a role in LPS nephropathy. Immunofluorescence colocalization analysis revealed a tight association of gammadeltaT cells with B7-1 in the kidney. High B7-1 expression was detected in podocytes treated with LPS. Podocytes cocultured with gammadeltaT 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. gammadeltaT 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. |
