Clinical and Translational Medicine (Mar 2024)

Interleukin‐2/anti‐interleukin‐2 immune complex attenuates cold ischemia‐reperfusion injury after kidney transplantation by increasing renal regulatory T cells

  • Joon Young Jang,
  • Hyung Woo Kim,
  • Ji‐Jing Yan,
  • Tae Kyeom Kang,
  • Wook‐Bin Lee,
  • Beom Seok Kim,
  • Jaeseok Yang

DOI
https://doi.org/10.1002/ctm2.1631
Journal volume & issue
Vol. 14, no. 3
pp. n/a – n/a

Abstract

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Abstract Background Cold ischemia‐reperfusion injury (IRI) is an unavoidable complication of kidney transplantation. We investigated the role of regulatory T cells (Treg) in cold IRI and whether the interleukin (IL)‐2/anti‐IL‐2 antibody complex (IL‐2C) can ameliorate cold IRI. Methods We developed a cold IRI mouse model using kidney transplantation and analyzed the IL‐2C impact on cold IRI in acute, subacute and chronic phases. Results Treg transfer attenuated cold IRI, while Treg depletion aggravated cold IRI. Next, IL‐2C administration prior to IRI mitigated acute renal function decline, renal tissue damage and apoptosis and inhibited infiltration of effector cells into kidneys and pro‐inflammatory cytokine expression on day 1 after IRI. On day 7 after IRI, IL‐2C promoted renal regeneration and reduced subacute renal damage. Furthermore, on day 28 following IRI, IL‐2C inhibited chronic fibrosis. IL‐2C decreased reactive oxygen species‐mediated injury and improved antioxidant function. When IL‐2C was administered following IRI, it also increased renal regeneration with Treg infiltration and suppressed renal fibrosis. In contrast, Treg depletion in the presence of IL‐2C eliminated the positive effects of IL‐2C on IRI. Conclusion Tregs protect kidneys from cold IRI and IL‐2C inhibited cold IRI by increasing the renal Tregs, suggesting a potential of IL‐2C in treating cold IRI. Key Points Interleukin (IL)‐2/anti‐IL‐2 antibody complex attenuated acute renal injury, facilitated subacute renal regeneration and suppressed chronic renal fibrosis after cold ischemia‐reperfusion injury (IRI) by increasing the renal Tregs. IL‐2/anti‐IL‐2 antibody complex decreased reactive oxygen species‐mediated injury and improved antioxidant function. This study suggests the therapeutic potential of the IL‐2/anti‐IL‐2 antibody complex in kidney transplantation‐associated cold IR.

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