Effect of uremic serum on Th17/Treg cell balance and endoplasmic reticulum stress in rats

The imbalance of T helper 17 (Th17) and regulatory T (Treg) cells exists in the occurrence and development of various diseases. Endoplasmic reticulum stress (ERS) is an important self-protective cellular response to harmful stimuli, such as uremic environment. The objective of this study was to investigate the Th17/Treg cell balance and ERS in a uremic environment and analyze the relationship between them.

(1) The rat spleen lymphocytes were extracted and treated with thapsigargin (inducer of ERS) and sodium citrate. The proportion of Th17 and Treg cells were then detected. (2) The uremic serum-cultured lymphocytes were used and divided into three groups: non-uremic serum group, uremic serum group, and uremic serum + sodium citrate group. Afterward, the proportion of Th17/Treg cells and the expression of ERS-related proteins (GRP78 and CHOP) were detected.

Thapsigargin had no significant effect on the proportion of Th17 cells within a limited concentration range, but it could reduce the proportion of Treg cells, sodium citrate had a negative influence on the deviation of Th17/Treg cells treated with thapsigargin. Uremic serum treatment reduced the proportion of Treg cells, resulting in an increase of the Th17/Treg ratio. However, sodium citrate had no influence on the deviation of Th17/Treg cells treated by uremic serum. Sodium citrate reduced the elevation of ERS-related proteins induced by uremic serum.

Uremic serum can lead to the imbalance of Th17/Treg cells as well as ERS, suggesting that ERS is one of the mechanisms of the imbalance of Th17/Treg cells induced by uremic serum. Sodium citrate can inhibit ERS induced by uremic serum.