ET A receptor activation contributes to T cell accumulation in the kidney following ischemia‐reperfusion injury

Renal ischemia‐reperfusion ( IR ) injury and acute kidney injury ( AKI ) increase the risk of developing hypertension, with T cells suspected as a possible mechanistic link. Endothelin promotes renal T cell infiltration in several diseases, predominantly via the ET A receptor, but its contribution to renal T cell infiltration following renal IR injury is poorly understood. To test whether ET A receptor activation promotes T cell infiltration of the kidney following IR injury, male C57 BL /6 mice were treated with the ET A receptor antagonist ABT ‐627 or vehicle, commencing 2 days prior to unilateral renal IR injury. Mice were sacrificed at 24 h or 10 days post‐ IR for assessment of the initial renal injury and subsequent infiltration of T cells. Vehicle and ABT ‐627‐treated mice displayed significant upregulation of endothelin‐1 ( ET ‐1) in the IR compared to contralateral kidney at both 24 h and 10 days post‐ IR ( P  <   0.001). Renal CD 3 + T cell numbers were increased in the IR compared to contralateral kidneys at 10 days, but ABT ‐627‐treated mice displayed a 35% reduction in this effect in the outer medulla ( P  <   0.05 vs. vehicle) and a nonsignificant 23% reduction in the cortex compared to vehicle‐treated mice. Whether specific T cell subsets were affected awaits confirmation by flow cytometry, but outer medullary expression of the T helper 17 transcription factor ROR γt was reduced by ABT ‐627 ( P  =   0.06). These data indicate that ET ‐1 acting via the ET A receptor contributes to renal T cell infiltration post‐ IR injury. This may have important implications for immune system‐mediated long‐term consequences of AKI , an area which awaits further investigation.