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IL-2/IL-2Ab complexes induce regulatory T cell expansion and protect against proteinuric CKD

Abstract

Regulatory T cells (Tregs) help protect against autoimmune renal injury. The use of agonist antibodies and antibody/cytokine combinations to expand Tregs in vivo may have therapeutic potential for renal disease. Here, we investigated the effects of administering IL-2/IL-2Ab complexes in mice with adriamycin nephropathy, a model of proteinuric kidney disease that resembles human focal segmental glomerulosclerosis. Injecting IL-2/IL-2Ab complexes before or, to a lesser extent, after induction of disease promoted expansion of Tregs. Furthermore, administration of this complex was renoprotective, evidenced by improved renal function, maintenance of body weight, less histologic injury, and reduced inflammation. IL-2/IL-2Ab reduced serum IL-6 and renal expression of IL-6 and IL-17 but enhanced expression of IL-10 and Foxp3 in the spleen. In vitro, the addition of IL-2/IL-2Ab complexes induced rapid STAT-5 phosphorylation in CD4 T cells. In summary, these data suggest that inducing the expansion of Tregs by administering IL-2/IL-2Ab complexes is a possible strategy to treat renal disease.

Type Journal
Authors Polhill, T.; Zhang, G. Y.; Hu, M.; Sawyer, A.; Zhou, J. J.; Saito, M.; Webster, K. E.; Wang, Y.; Wang, Y.; Grey, S. T.; Sprent, J.; Harris, D. C.; Alexander, S. I.; Wang, Y. M.;
Garvan Authors Prof Jonathan Sprent , Dr Kylie Webster , A/Prof Shane Grey
Publisher Name J AM SOC NEPHROL
Published Date 2012-06-09 00:00:00
Published Volume 23
Published Issue 8
Published Pages 1303-8
URL http://www.ncbi.nlm.nih.gov/pubmed/22677553
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?11433_12988/12_Polhill_J Am Soc Nephrol.pdf