IL-2/IL-2Ab Complexes Induce Regulatory T Cell Expansion and Protect Against Proteinuric CKD

Overview

Journal J Am Soc Nephrol

Specialty Nephrology

Date 2012 Jun 9

PMID 22677553

Citations 32

Authors

Tania Polhill

Geoff Yu Zhang

Min Hu

Andrew Sawyer

Jimmy Jianheng Zhou

Mitsuru Saito

Kylie E Webster

Ya Wang

Yiping Wang

Shane T Grey

Jonathan Sprent

David C H Harris

Stephen I Alexander

Yuan Min Wang

Affiliations

Soon will be listed here.

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.

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