Interleukin-17 Deficiency Attenuates Renal Allograft Injury and Prolongs Survival in a Murine Transplantation Model

T. Kwan,^1,2 S. Chadban,^1,2 J. Ma,^1,2 S. Bao,^2,3 S. Alexander,^2,4 H. Wu.^1,2

¹Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
²Renal Medicine, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
³Discipline of Pathology, School of Medical Sciences, Sydney, New South Wales, Australia
⁴Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.

Meeting: 2015 American Transplant Congress

Abstract number: D74

Keywords: Kidney transplantation, knockout, Mice, Rejection

Session Information

Session Name: Poster Session D: Innate Immunity in Transplantation

Session Type: Poster Session

Date: Tuesday, May 5, 2015

Session Time: 5:30pm-6:30pm

Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

Aim:

To investigate the role of IL-17 in allograft rejection using a murine model of fully MHC-mismatched renal transplantation.

Methods:

Life-sustaining kidney transplants were performed in nephrectomized mice: WT BALB/c to WT C57BL/6 (WT allografts), IL-17^-/- BALB/c to IL-17^-/- C57BL/6 (IL-17^-/- allografts) and WT C57BL/6 to WT C57BL/6 (isografts). Mice were also sacrificed on days 14 and 100 post-transplantation for assessment of the acute and chronic rejection responses.

Results:

IL-17^-/- allograft recipients had significantly improved survival as compared to WT allograft recipients (median survival >100 vs 37.5 days, p=0.031). Similar prolongation was achieved in WT allografts which received a neutralizing IL-17 antibody (median survival >100 days, p=0.027). IL-17^-/- allografts were protected against acute rejection with lower serum creatinine (26.22±1.75 vs 50.00±4.42μmol/L, p=0.0018) and less tubulitis (score 109.6±7.66 vs 158.3±9.65, p=0.0007) compared to WT allografts and isolated T cells produced less IFN-γ in response to ex vivo allostimulation (p<0.0001). By day 100, IL-17^-/- allografts exhibited superior renal function (20.00±3.01 vs 48.75±9.48μmol/L, p=0.025), less proteinuria (0.41±0.20 vs 1.13±0.10mg/16hrs, p=0.0095) and reduced interstitial collagen deposition (13.48±2.49 vs 30.37±4.09% points positive, p=0.0082) compared to WT allografts. Subsequent experiments using either donors or recipients deficient in IL-17 showed a trend towards prolongation of survival only when the recipients were IL-17^-/-. The survival advantage conferred by IL-17 deficiency was attenuated by depletion of CD4⁺CD25⁺ cells.

Conclusion:

Renal allograft rejection was attenuated, survival prolonged and long term graft function improved in the absence of IL-17. This is likely due to impaired development of Th1 alloimmunity and is CD4⁺CD25⁺ dependent.

To cite this abstract in AMA style:

Kwan T, Chadban S, Ma J, Bao S, Alexander S, Wu H. Interleukin-17 Deficiency Attenuates Renal Allograft Injury and Prolongs Survival in a Murine Transplantation Model [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/interleukin-17-deficiency-attenuates-renal-allograft-injury-and-prolongs-survival-in-a-murine-transplantation-model/. Accessed November 23, 2024.

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