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

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dc.contributor.authorPolhill, T.
dc.contributor.authorZhang, G.Y.
dc.contributor.authorHu, M.
dc.contributor.authorSawyer, A.
dc.contributor.authorZhou, J.J.
dc.contributor.authorSaito, M.
dc.contributor.authorWebster, K.E.
dc.contributor.authorWang, Y.
dc.contributor.authorWang, Y.
dc.contributor.authorGrey, S.T.
dc.contributor.authorSprent, J.
dc.contributor.authorHarris, D.C.H.
dc.contributor.authorAlexander, S.I.
dc.contributor.authorWang, Y.M.
dc.date.issued2012
dc.description.abstractRegulatory 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.
dc.description.statementofresponsibilityTania Polhill, Geoff Yu Zhang, Min Hu, Andrew Sawyer, Jimmy Jianheng Zhou ... Shane T. Grey ... et al.
dc.identifier.citationJournal of the American Society of Nephrology, 2012; 23(8):1303-1308
dc.identifier.doi10.1681/ASN.2011111130
dc.identifier.issn1046-6673
dc.identifier.issn1533-3450
dc.identifier.orcidGrey, S.T. [0000-0003-2160-1625]
dc.identifier.urihttp://hdl.handle.net/2440/121152
dc.language.isoen
dc.publisherAmerican Society of Nephrology
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/571343
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/632519
dc.rights© 2012 by the American Society of Nephrology
dc.source.urihttps://doi.org/10.1681/asn.2011111130
dc.subjectT-Lymphocytes, Regulatory
dc.titleIL-2/IL-2Ab complexes induce regulatory T cell expansion and protect against proteinuric CKD
dc.typeJournal article
pubs.publication-statusPublished

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