Kidney Week

Abstract: TH-PO042

Characterization of Regulatory B Cells and IL-10 in Response to Ischemic Reperfusion and Potential for Infusion Therapy

Session Information

• AKI: Epidemiology, Risk Factors, and Prevention - 1
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 101 AKI: Epidemiology, Risk Factors, and Prevention

Authors

• Yamashita, Yuya, Kurume Daigaku, Kurume, Fukuoka, Japan

Yuya Yamashita, MD

• Taguchi, Kensei, Kurume Daigaku, Kurume, Fukuoka, Japan

Kensei Taguchi, MD, PhD

• Yokota, Yunosuke, Kurume Daigaku, Kurume, Fukuoka, Japan

Yunosuke Yokota, MD

• Moriyama, Tomofumi, Kurume Daigaku, Kurume, Fukuoka, Japan

Tomofumi Moriyama, MD, PhD

• Fukami, Kei, Kurume Daigaku, Kurume, Fukuoka, Japan

Kei Fukami, MD, PhD

Background

Acute kidney injury (AKI) occurs in approximately 15% of hospitalized patients and it predisposes the patients to chronic kidney disease (CKD). Interleukin-10 (IL-10) is a pleiotropic cytokine, and exogenous IL-10 replacement therapy is renoprotective effect against AKI. However, the required concentration of IL-10 seems not feasible to achieve when applied to human. Subpopulation of B cells presenting with CD1dhiCD5+ (regulatory B cells; Breg) are known to be responsible for producing and secreting IL-10. Thus, in the present study, we investigated the role of Breg and the main sources in AKI. Further, we investigated whether exogenous Breg would adhere in the kidneys of the recipients and prevent the AKI-to-CKD transition.

Methods

IL10⁺/eGFP mice were employed to trace IL-10-producing Breg in the context of AKI. Ischemia-reperfusion (IR)-AKI was induced in IL10⁺/eGFP mice and the number of GFP-labelled Breg were evaluated in several organs, such as kidneys and spleens. Subpopulation of B-1 cells isolated from peritoneal cavity of IL10⁺/eGFP mice were infused into wild-type mice with IR-AKI to examine whether exogenous regulatory B cells adhere to the injured kidneys. Third, spleens, the main source of Breg, were removed before IR-AKI to explore whether deletion of Breg exacerbates AKI in IL10⁺/eGFP mice.

Results

The number of GFP+ Breg was increased in the spleens 24 hrs after onset of IR-AKI. The number of GFP+ Breg was increased in the kidneys with the upregulation of IL-10 gene expression on day7 and 14 after IR-AKI. Furthermore, when GFP+ B-1 cells were exogenously infused, we identified GFP+ cells in kidneys of wild-type mice with IR-AKI, the number of which was increased in injured kidneys. Splenectomy in the context of AKI reduced the number of GFP+ cells in kidneys of IR-AKI with the reduction in gene expression of IL-10. Renal dysfunction and tubular damage in IR-AKI were worsened by splenectomy and immune cells infiltration, such as CD68+ microphages and CD3+ T cells, were enhanced.

Conclusion

We identified that IL-10-producing Breg were mainly released from the spleens in response to IR-AKI, which may be involved in repair process after IR-AKI via producing IL-10. In addition, the infusion with autologous Breg might be potent to promote proper repair and prevent AKI-to-CKD.