Abstract: SA-PO0129
Regulatory B Cell-Targeted Therapeutic Interventions Against AKI-to-CKD Transition
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
- Yamashita, Yuya, Kurume Daigaku, Kurume, Fukuoka Prefecture, Japan
- Taguchi, Kensei, Kurume Daigaku, Kurume, Fukuoka Prefecture, Japan
- Yokota, Yunosuke, Kurume Daigaku, Kurume, Fukuoka Prefecture, Japan
- Fukami, Kei, Kurume Daigaku, Kurume, Fukuoka Prefecture, Japan
Background
Acute kidney injury (AKI) occurs in 20% of hospitalized patients and predisposes the patients to chronic kidney disease (CKD). B cells presenting with CD1dhiCD5+ are recognized as regulatory B cells (Bregs), which can produce and secrete interleukin-10 (IL-10). IL-10 is an anti-inflammatory cytokine and its administration has shown renoprotective effects against AKI. However, a large amount of IL-10 would be required to reach therapeutic concentrations in humans. To explore the potential of Bregs as a therapeutic strategy, we investigated how AKI affects Breg proliferation and examined whether Bregs infusion and in vivo induction prevent AKI-to-CKD transition.
Methods
IL10+/eGFP mice were employed to track IL-10-producing Bregs in ischemic reperfusion (IR)-AKI and GFP+ Bregs were quantified in organs, including kidney and spleen at different time points. B1a cells, a major population of IL-10-producing B cells, were isolated from IL10+/eGFP mice and transferred into wild-type mice subject to IR-AKI to assess their renal infiltration and reno-protective effects. To explore whether deletion of splenic Bregs exacerbates the AKI-to-CKD, splenectomy was performed. Additionally, to evaluate in vivo induction of Bregs, we performed vagus nerve stimulation (VNS) before IR-AKI.
Results
Splenic GFP+ Bregs markedly increased at 24 hours following IR-AKI, whereas renal GFP+ Bregs accumulated on day 7 and 14 after IR-AKI in parallel with increased IL-10 gene expression. Adoptive transfer of GFP+B1a cells led to enhanced accumulation of GFP+ cells in both the spleen and injured kidneys of wild-type mice compared to the uninjured controls. Splenectomy prior to IR-AKI reduced the number of GFP+ Bregs in the AKI kidneys accompanied by the decrease in renal IL-10. Splenic Bregs deficiency worsened tubular injury and kidney fibrosis with the increase in cytotoxic immune cells infiltration. Furthermore, VNS prior to IR-AKI promoted splenic B cells expansion and increased GFP+ Bregs in the AKI kidneys, and improved tubular injury, immune cells activation, and kidney fibrosis.
Conclusion
Splenic Bregs are involved in proper kidney repair via promoting immune tolerance and attenuating tubular injury and fibrosis following IR-AKI. Adoptive transfusion with autologous Bregs or in vivo induction of Breg represents a potent therapeutic strategy to prevent the AKI-to-CKD.