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- Title
Regulatory T cells participate in CD39-mediated protection from renal injury.
- Authors
Wang, Yuan Min; McRae, Jennifer L.; Robson, Simon C.; Cowan, Peter J.; Zhang, Geoff Yu; Hu, Min; Polhill, Tania; Wang, Yiping; Zheng, Guoping; Wang, Ya; Lee, Vincent W.S.; Unwin, Robert J.; Harris, David C.H.; Dwyer, Karen M.; Alexander, Stephen I.
- Abstract
CD39 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 ( Treg) 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 CD39-transgenic (h CD39 Tg) and wild-type ( WT) BALB/c mice. Effects of CD39 expression by Treg cells were assessed in AN by adoptive transfer of CD4+ CD25+ and CD4+ CD25− T cells isolated from h CD39 Tg and WT mice. h CD39 Tg 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 CD25+ and h CD39 Tg CD25− T cells conferred some protection against AN, h CD39 Tg CD25+ Treg cells offered greater protection. In vitro studies showed direct pro-apoptotic effects of ATP on renal tubular cells. In conclusion, h CD39 expressed by circulating leukocytes and intrinsic renal cells limits innate AN injury. Specifically, CD39 expression by Treg cells contributes to its protective role in renal injury. These findings suggest that extracellular nucleotides mediate AN kidney injury and that CD39, expressed by Treg cells and other cells, is protective in this model.
- Publication
European Journal of Immunology, 2012, Vol 42, Issue 9, p2441
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201242434