Abstract: TH-OR52
IL-2/Anti-IL-2 Immune Complex Attenuates Cold Ischemia-Reperfusion Injury in Kidney Transplantation by Expanding Regulatory T Cells
Session Information
- Transplantation: Basic Research
November 03, 2022 | Location: W314, Orange County Convention Center‚ West Building
Abstract Time: 05:06 PM - 05:15 PM
Category: Transplantation
- 2001 Transplantation: Basic
Authors
- Heo, Ga Young, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
- Jang, Joon Young, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
- Koo, Tai yeon, Korea University Medical Center, Seoul, Korea (the Republic of)
- Koh, Hee Byung, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
- Kim, Hyo Jeong, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
- Kim, Beom Seok, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
- Yang, Jaeseok, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
Background
Renal cold ischemia-reperfusion injury (IRI) is an inevitable complication after kidney transplantation and a more severe inflammatory response than renal warm IRI. We investigated role of regulatory T cells (Tregs) in cold renal IRI and whether Treg-expanding IL-2/anti-IL-2 complex (IL-2C) can attenuate renal cold IRI.
Methods
We used a mouse cold IRI model based on kidney transplantation along with Foxp3-DTR mouse to deplete Tregs. We investigated impact of IL-2C on acute, subacute, and chronic phase of cold IRI as well as role of Tregs.
Results
Cold IRI induced more severe renal functional deterioration, renal tissue damage and fibrosis than warm IRI. Mortality after cold IRI increased as cold ischemic time became longer than 6hr. Adoptive transfer of Tregs successfully attenuated cold IRI. In parallel, administration of IL-2C, a Treg expander before cold IRI, attenuated acute renal functional deterioration, renal tissue injury and apoptosis, and suppressed renal infiltration of effector cells along with expression of pro-inflammatory cytokines. IL-2C also attenuated subacute renal injury and facilitated renal regeneration on day 7 after cold IRI. Furthermore, IL-2C suppressed chronic fibrosis and epithelial mesenchymal transition along with renal infiltration of SMA+F4/80+CD11b+ profibrotic macrophages on day 28 after cold IRI. ROS injury was also attenuated by IL-2C, as expression levels of Nox2, 8-OHG, MDA, and nitrotyrosine were decreased with increased expression of SOD and GSH. On the other hand, depletion of Tregs using diphtheria toxin in the presence of IL-2C, abrogated the beneficial effects of IL-2C on cold IRI.
Conclusion
Tregs play protective roles in renal cold IRI. IL-2C attenuated acute injury, facilitated subacute recovery, and suppressed chronic fibrosis in renal cold IRI through expansion of renal Tregs, suggesting the therapeutic potential of IL-2C in kidney transplantation-associated cold IRI.