IL-2/IL-2Ab complexes induce regulatory T cell expansion and protect against proteinuric CKD.
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.
Centre for Kidney Research, Children's Hospital at Westmead, Westmead NSW 2145, Sydney, Australia.
Tania
T
Polhill
Geoff Yu
GY
Zhang
Min
M
Hu
Andrew
A
Sawyer
Jimmy Jianheng
JJ
Zhou
Mitsuru
M
Saito
Kylie E
KE
Webster
Ya
Y
Wang
Yiping
Y
Wang
Shane T
ST
Grey
Jonathan
J
Sprent
David C H
DC
Harris
Stephen I
SI
Alexander
Yuan Min
YM
Wang
D000818:Animals; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D004317:Doxorubicin; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000517:prevention & control*; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011507:Proteinuria / Q000139:chemically induced / Q000517:prevention & control*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D004317:Doxorubicin