To investigate the effect of depleting renal natural killer (NK) cells on folic acid-induced acute kidney injury (AKI) in mice.

Male C57BL/6J mice aged 8-10 weeks old were selected and randomly divided into the following groups (n=5 per group): a model group (intraperitoneal injection of folic acid at 250 mg/kg), a model+ anti-mouse IgG2a antibody group (intraperitoneal injection of 200 μg IgG2a antibody for 2 consecutive days prior to modeling), a model+ anti-mouse NK1.1 antibody group (intraperitoneal injection of 200 μg anti-NK1.1 antibody for 2 consecutive days prior to modeling), and a control group (intraperitoneal injection of an equivalent volume of 0.3 M NaHCO₃). Mice of the control and model groups were sacrificed 2 days after modeling to evaluate serum creatinine, blood urea nitrogen, kidney-to-body weight ratio, and renal histopathological changes. Flow cytometry was performed to analyze the proportions of CD4⁺ T cells, CD8⁺ T cells, regulatory T cells, and NK cells in kidney tissues, as well as their capacity to secrete cytokines as interleukin-17A, interferon-γ, and tumor necrosis factor-α. For the model+ anti-mouse IgG2a antibody group and the model+ anti-mouse NK1.1 antibody group, the renal NK cells depletion efficiency was assessed by flow cytometry 2 days after modeling, along with the analysis of renal function and observation of renal pathological changes.

Compared with the control group, the model group showed significantly higher serum creatinine and blood urea nitrogen levels, as well as more severe renal tissue injury (all P<0.05), while the proportion of NK cells in the kidneys was also significantly increased (P<0.05), accompanied by decreased interferon-γ and increased tumor necrosis factor-α secretion (all P<0.05). In contrast, the proportions of CD4⁺ T cells, CD8⁺ T cells, and regulatory T cells, along with their associated cytokines, showed no significant changes in the renal tissues. Compared with the model+ anti-mouse IgG2a antibody group, the model + anti-mouse NK1.1 antibody group exhibited significant renal NK cells depletion, accompanied by lower serum creatinine and blood urea nitrogen levels and attenuated renal tissue injury (all P<0.05).

The use of anti-mouse NK1.1 antibody significantly depleted NK cells in renal tissues and attenuated folic acid-induced AKI in mice, suggesting that its protective mechanism is associated with reduced NK cells infiltration and decreased pro-inflammatory cytokines secretion in the kidneys.