File(s) under permanent embargo
Regulatory T cells participate in CD39-mediated protection from renal injury
journal contribution
posted on 2012-09-01, 00:00 authored by Yuan Min Wang, Jennifer L McRae, Simon C Robson, Peter J Cowan, Geoff Yu Zhang, Min Hu, Tania Polhill, Yiping Wang, Guoping Zheng, Ya Wang, Vincent W S Lee, Robert J Unwin, David C H Harris, Karen DwyerKaren Dwyer, Stephen I AlexanderCD39 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 (hCD39Tg) 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 hCD39Tg and WT mice. hCD39Tg 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 hCD39Tg CD25(-) T cells conferred some protection against AN, hCD39Tg CD25(+) Treg cells offered greater protection. In vitro studies showed direct pro-apoptotic effects of ATP on renal tubular cells. In conclusion, hCD39 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.
History
Journal
European journal of immunologyVolume
42Issue
9Pagination
2441 - 2451Publisher
WileyLocation
London, Eng.Publisher DOI
eISSN
1521-4141Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2012, WileyUsage metrics
Categories
Keywords
Adenosine TriphosphateAnimalsAntigens, CDApoptosisApyraseCreatinineDisease Models, AnimalDoxorubicinHumansKidney DiseasesKidney TubulesLeukocytesMaleMiceMice, Inbred BALB CMice, TransgenicT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryScience & TechnologyLife Sciences & BiomedicineImmunologyAdriamycin nephropathy (AN)ATPCD39Foxp3Treg cellsINNATE IMMUNE RECOGNITIONP2X(7) RECEPTOREXTRACELLULAR ATPISCHEMIA-REPERFUSIONLUNG INFLAMMATIONHUMAN CD39EXPRESSIONADENOSINEKIDNEYMOUSEImmunology
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC