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Abstract: SA-PO066

CD8+CD103+ iTregs Attenuate Ischemia-Reperfusion AKI by Suppressing Pyroptosis

Session Information

  • AKI: Mechanisms - III
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Chen, Qiuju, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
  • Xu, Zhenjian, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
  • Zhang, Xiao, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
  • Xu, Anping, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
Background

Acute kidney injury (AKI) is a disease related to high morbidity, mortality and healthcare costs. It has been reported that there is strong inflammation in AKI. However, specific or effective treatment for AKI hasn’t been established at present. Previously, we have reported that CD8+CD103+ Treg induced ex vivo with TGF-β1 and IL-2 (CD8+CD103+ iTreg) inhibited response of immune cells to ameliorate excessive autoimmune inflammation. Here, we further explore whether CD8+CD103+ iTreg can ameliorate AKI and determine the potential molecular mechanism.

Methods

In vivo, we used mouse model of ischemia-reperfusion injury to investigate whether CD8+CD103+ iTreg can attenuate AKI by protecting tubular epithelial cells. In vitro, we co-cultured tubular cells with CD8+CD103+ iTreg to explore the mechanism of Treg for protecting against renal I/R injury.

Results

Adoptive transfer of CD8+CD103+ iTreg but not control cells to the mice of ischemia-reperfusion injury showed decreased levels of serum creatinine and blood urea nitrogen, reduced tissue injury, and lowered tubular apoptosis. Additionally, CD8+CD103+ iTreg treatment decreased infiltration of macrophages and T cells as well as renal levels of IL-6, IL-1β, TNF-α, and IFN-γ, but it increased levels of IL-10, arginase-1. Moreover, administering CD8+CD103+ iTreg after ischemia-reperfusion injury limited the number of pyroptotic cells. In vitro, CD8+CD103+ iTreg reversed hypoxia/reoxygenation-induced cell injury partly by suppressing tubular cell pyroptosis via inhibiting the NLRP3/Caspase-1 axis.

Conclusion

CD8+CD103+ iTreg suppressed tubular epithelial cell pyroptosis to attenuate AKI after ischemia-reperfusion injury. Our data suggests therapeutic potential of CD8+CD103+ iTreg in renal ischemia-reperfusion injury.

Fig1.CD8+CD103+ iTregs protect against AKI in mice.

Funding

  • Government Support – Non-U.S.