Delayed ischaemic preconditioning in the presence of galectin-9 protects against renal ischaemic injury through a regulatory T-cell dependent mechanism.

ABSTRACT

AIM: Renal ischaemia/reperfusion injury (IRI) is a complication of major surgeries. Regulatory T cells (Tregs) can suppress immunologic damage in the renal IR. Previous studies indicated that delayed ischaemic preconditioning (IPC) partially attenuates IR by inducing Treg expansion. Galectin-9 also attenuates inflammation-related organ injury by expanding Tregs, but it was not used in renal IR yet. Our aim was to test whether IPC combined with galectin-9 has an increased renoprotective effect. METHODS: Mice were divided into five treatment groups (n = 6 per group) (i) IR group renal ischaemia/reperfusion group; (ii) IPC-IR group IPC followed by renal IR; (iii) IPC-Gal9-IR group Gal-9 injections during the time between IPC and IR; (iv) IPC-Gal9-PC61-IR group anti-CD25 antibody administration apart from IPC, Gal-9 and IR; (v) sham-sham group. We assessed the renal function, histopathological scores, and percentages of Tregs and interferon-γ (IFN-γ) cells in peripheral bood, spleen, and kidney and compared these values among the different groups. RESULTS: Serum creatinine measured was significantly lower after IPC and even lower in combination with Gal-9 injection. The histopathological scores for tubulo-interstitial injury were decreased following IPC and markedly lower after the addition of Gal-9. The number of kidney infiltrating neutrophils and IFN-γ secreting CD4+ T cells was diminished in the IPC/Gal9 combination group, while the percentage of Treg cells in the peripheral blood, spleen, and kidney of animals from the IPC-Gal9-IR group was also markedly increased. CONCLUSION: The renoprotective effect of delayed IPC combined with galectin-9 was superior to IPC alone, through a mechanism related to expansion of regulatory T cells.