Objective:

To investigate the effects of multiple cytokines on the level of regulatory T cells (Tregs) in children with idiopathic nephrotic syndrome (INS).

Approach:

• Sample Collection: Blood samples were collected from children with INS before and after glucocorticoid therapy and from age-matched healthy controls.
• Flow Cytometry Analysis: The proportions of CD4+CD25+FOXP3+ Tregs were analyzed by flow cytometry.
• Cytokine Measurement: Plasma concentrations of TNF-α, IL-1β, and IL-2 were measured using a cytometric bead array.
• PCR Analysis: Real-time polymerase chain reaction (PCR) was used to detect levels of Treg-associated factors and signaling molecules in CD4+CD25+ T cells.

Key Findings:

• Children with active INS showed significantly decreased proportions of Tregs and reduced expression of FOXP3, GITR, and CTLA-4 (all P < 0.05).
• Elevated plasma levels of TNF-α, IL-1β, and IL-2 were observed in children with active INS (all P < 0.05).
• Expression of TNFRII, HIF1α, PI3K, AKT, and mTOR was significantly increased in the active INS group (all P < 0.05).
• Glucocorticoid treatment partially restored Treg abnormalities.
• TNF-α/TNFRII signaling was negatively correlated with FOXP3 expression.

Interpretation:

Increased levels of TNF-α in patients with active INS downregulated FOXP3 and led to overexpression of TNFRII.

Limitations:

• The study did not explore the cellular sources of elevated cytokines in active INS.
• The sample size was limited to 40 children.

Conclusion:

Aberrant signaling pathways in INS may contribute to the downregulation of FOXP3+ Tregs.