Regulatory T cells participate in CD 39‐mediated protection from renal injury

CD 39 is an ecto‐enzyme that degrades extracellular nucleotides, such as ATP , and is highly expressed on by the vasculature and circulating cells including Foxp3 + regulatory T ( T reg) cells. To study the role of purinergic regulation in renal disease, we used the adriamycin nephropathy ( AN ) mouse model of chronic renal injury, using human CD 39‐transgenic (h CD 39 T g) and wild‐type ( WT ) BALB /c mice. Effects of CD 39 expression by T reg cells were assessed in AN by adoptive transfer of CD 4 + CD 25 + and CD 4 + CD 25 − T cells isolated from h CD 39 T g and WT mice. h CD 39 T g mice were protected from renal injury in AN with decreased urinary protein and serum creatinine, and significantly less renal injury compared with WT mice. While WT CD 25 + and h CD 39 T g CD 25 − T cells conferred some protection against AN , h CD 39 T g CD 25 + T reg cells offered greater protection. In vitro studies showed direct pro‐apoptotic effects of ATP on renal tubular cells. In conclusion, h CD 39 expressed by circulating leukocytes and intrinsic renal cells limits innate AN injury. Specifically, CD 39 expression by T reg cells contributes to its protective role in renal injury. These findings suggest that extracellular nucleotides mediate AN kidney injury and that CD 39, expressed by T reg cells and other cells, is protective in this model.