Abstract: SA-PO0135
β-Catenin Lactylation in ST2 Tregs Regulates IFN-γ/IL-10 to Promote Kidney Repair After Cardiac Surgery-Associated AKI
Session Information
- AKI: Mechanisms - 3
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Hao, Zhang, Nanjing First Hospital, Nanjing, Jiangsu, China
- Ma, Mengqing, Nanjing First Hospital, Nanjing, Jiangsu, China
- Wan, Xin, Nanjing First Hospital, Nanjing, Jiangsu, China
- Cao, Changchun, Sir Run Run Hospital Nanjing Medical University, Nanjing, Jiangsu, China
Background
Acute kidney injury (AKI) represents the most frequent complication after cardiac surgery. Regulatory T cells (Tregs) is a the most potent immunosuppressive cells that was shown to protect the heart from myocardial ischemia- reperfusion injury, but its role in the pathogenesis of AKI remains unknown. This study aims to investigate that β-catenin lactylation in ST2+ Tregs regulates their functional polarization to mediate CSA-AKI recovery.
Methods
Peripheral blood mononuclear cells (PBMCs) and clinical data were collected from cardiac surgery patients (2022–2024, Nanjing First Hospital). Flow cytometry was employed to analyzed dynamic changes in ST2+ Treg subsets. serum samples were collected to measure lactate levels and the concentrations of IFN-γ and IL-10 during the recovery phase. We used murine renal ischemia-reperfusion injury to delineate the role of the ST2 specifically in Treg cells using targeted deletion. Bulk and single-cell RNA sequencing was performed on flow-sorted Tregs from spleen and CD4 T-cells from post-ischemic kidneys respectively. The protective role of ST2-sufficient Tregs was analyzed using adoptive transfer. Co-immunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP), and luciferase assays were conducted to determined that β-catenin/HDAC1 transcriptional repression complexes regulate IFN-γ and IL-10 transcription.
Results
We showed that ST2+ Tregs were highly enriched in CSA-AKI patients. Compared with healthy donors, produced more IFN-γ and less IL-10, and the ratio of IFN-γ- to IL-10-producing Treg cells further highlighted this imbalance. Treg-specific deletion of ST2 exacerbated kidney injury in the ischemia reperfusion injury model. Lactate accumulation induced lactylation at β-catenin K26, disrupting HDAC1 binding and thereby relieving IL-10 suppression. This modification drove ST2+ Tregs toward a reparative ST2+IL10+ phenotype.
Conclusion
Lactate accumulation triggers β-catenin lactylation, which disrupts β-catenin/HDAC1 complexes, alleviates IL-10 suppression, and promotes ST2+IL-10+ Treg polarization, enhancing renal repair after CSA-AKI.