#1175 Regulatory T cells: a promising therapeutic strategy for AKI

Abstract Background and Aims Inflammation plays a crucial role in the injury and repair process following acute kidney injury (AKI). This involves complex interactions between myeloid and lymphoid immune cell subpopulations, and kidney parenchymal cells. However, severe, or persistent AKI can lead to incomplete or maladaptive repair, characterized by prolonged inflammation and continuous tissue damage resulting in CKD or kidney failure. Further research in this field is essential to understand the interplay between pro- and anti-inflammatory actions of immune cell populations in the pathogenesis and progression of kidney diseases. In the current study we aim to assess the therapeutic potential of regulatory T cells (Tregs), a specialized CD4+ lymphoid subpopulation with anti-inflammatory capacity, in acute kidney disease. Method C57BL/6J male mice 9 weeks old were intraperitoneally (i.p.) injected with 12.5 mg/kg cisplatin to induce AKI and treated after 24 hours with a single intravenous injection (i.v.) of 3 × 106 murine regulatory T cells (CD4+ CD25+), expanded ex vivo. Plasma Creatinine, Blood Urea Nitrogen (BUN) and Kidney Injury markers, KIM-1 and NGAL were analysed. Further work with qPCR and MSD analysis, were used to characterise kidney immune cell subpopulations and cytokine profiles. Results Cisplatin-induced AKI mice, treated with Tregs 24 hours after AKI induction showed a significant reduction in plasma Creatinine and BUN levels compared to control mice, as well as decreased excretion of urinary kidney injury markers KIM1 and NGAL. Interestingly, we saw an increase of FOXP3 and CD4 gene expression in kidney tissue, but no effect on IL-6, IL-1b, TNF-α, CCL2 pro-inflammatory cytokines, in plasma, urine and kidney, after Treg transfer, despite potent benefit on kidney function. Further analyses are ongoing to characterize the kidney immune cell and full cytokine landscape. Conclusion This data indicates the potential therapeutic efficacy of enhanced anti-inflammatory actions of regulatory T cells in an acute kidney injury mouse model. This data suggests that targeting or the use of Tregs as a promising therapeutic intervention strategy for AKI.