Interleukin-2/anti-interleukin-2 Immune Complex Attenuates Cold Ischemia-reperfusion Injury After Kidney Transplantation by Increasing Renal Regulatory T Cells

Overview

Journal Clin Transl Med

Publisher Wiley

Specialty General Medicine

Date 2024 Mar 20

PMID 38504554

Authors

Joon Young Jang

Hyung Woo Kim

Ji-Jing Yan

Tae Kyeom Kang

Wook-Bin Lee

Beom Seok Kim

Jaeseok Yang

Affiliations

Soon will be listed here.

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.

Citing Articles

Machine Perfusion and Bioengineering Strategies in Transplantation-Beyond the Emerging Concepts.

Niroomand A, Nita G, Lindstedt S Transpl Int. 2024; 37:13215.

PMID: 39267617 PMC: 11390383. DOI: 10.3389/ti.2024.13215.

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

Jang J, Kim H, Yan J, Kang T, Lee W, Kim B Clin Transl Med. 2024; 14(3):e1631.

PMID: 38504554 PMC: 10951489. DOI: 10.1002/ctm2.1631.

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