γδT Cells Exacerbate Podocyte Injury via the CD28B7-1-Phosphor-SRC Kinase Pathway

الملخص EN

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.