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

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

doi:10.1681/ASN.2011111130

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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

48 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1303-1308
Number of pages	6
Journal	Journal of the American Society of Nephrology
Volume	23
Issue number	8
DOIs	https://doi.org/10.1681/ASN.2011111130
Publication status	Published - Aug 2012
Externally published	Yes

Keywords

VERSUS-HOST-DISEASE
IN-VIVO EXPANSION
MONOCLONAL-ANTIBODY
AUTOIMMUNE-DISEASE
CUTTING EDGE
IMMUNOTHERAPY
IL-2
INTERLEUKIN-2
TOLERANCE
CANCER

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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. H., Alexander, S. I., & Wang, Y. M. (2012). IL-2/IL-2Ab complexes induce regulatory T cell expansion and protect against Proteinuric CKD. Journal of the American Society of Nephrology, 23(8), 1303-1308. https://doi.org/10.1681/ASN.2011111130

Polhill, Tania ; Zhang, Geoff Yu ; Hu, Min ; Sawyer, Andrew ; Zhou, Jimmy Jianheng ; Saito, Mitsuru ; Webster, Kylie E. ; Wang, Ya ; Wang, Yiping ; Grey, Shane T. ; Sprent, Jonathan ; Harris, David C. H. ; Alexander, Stephen I. ; Wang, Yuan Min. / IL-2/IL-2Ab complexes induce regulatory T cell expansion and protect against Proteinuric CKD. In: Journal of the American Society of Nephrology. 2012 ; Vol. 23, No. 8. pp. 1303-1308.

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title = "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.",

keywords = "VERSUS-HOST-DISEASE, IN-VIVO EXPANSION, MONOCLONAL-ANTIBODY, AUTOIMMUNE-DISEASE, CUTTING EDGE, IMMUNOTHERAPY, IL-2, INTERLEUKIN-2, TOLERANCE, CANCER",

author = "Tania Polhill and Zhang, {Geoff Yu} and Min Hu and Andrew Sawyer and Zhou, {Jimmy Jianheng} and Mitsuru Saito and Webster, {Kylie E.} and Ya Wang and Yiping Wang and Grey, {Shane T.} and Jonathan Sprent and Harris, {David C. H.} and Alexander, {Stephen I.} and Wang, {Yuan Min}",

year = "2012",

month = aug,

doi = "10.1681/ASN.2011111130",

language = "English",

volume = "23",

pages = "1303--1308",

journal = "Journal of the American Society of Nephrology",

issn = "1046-6673",

publisher = "Lippincott Williams & Wilkins",

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IL-2/IL-2Ab complexes induce regulatory T cell expansion and protect against Proteinuric CKD. / Polhill, Tania; Zhang, Geoff Yu; Hu, Min; Sawyer, Andrew; Zhou, Jimmy Jianheng; Saito, Mitsuru; Webster, Kylie E.; Wang, Ya; Wang, Yiping; Grey, Shane T.; Sprent, Jonathan; Harris, David C. H.; Alexander, Stephen I.; Wang, Yuan Min.

In: Journal of the American Society of Nephrology, Vol. 23, No. 8, 08.2012, p. 1303-1308.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - IL-2/IL-2Ab complexes induce regulatory T cell expansion and protect against Proteinuric CKD

AU - Polhill, Tania

AU - Zhang, Geoff Yu

AU - Hu, Min

AU - Sawyer, Andrew

AU - Zhou, Jimmy Jianheng

AU - Saito, Mitsuru

AU - Webster, Kylie E.

AU - Wang, Ya

AU - Wang, Yiping

AU - Grey, Shane T.

AU - Sprent, Jonathan

AU - Harris, David C. H.

AU - Alexander, Stephen I.

AU - Wang, Yuan Min

PY - 2012/8

Y1 - 2012/8

N2 - 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.

AB - 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.

KW - VERSUS-HOST-DISEASE

KW - IN-VIVO EXPANSION

KW - MONOCLONAL-ANTIBODY

KW - AUTOIMMUNE-DISEASE

KW - CUTTING EDGE

KW - IMMUNOTHERAPY

KW - IL-2

KW - INTERLEUKIN-2

KW - TOLERANCE

KW - CANCER

U2 - 10.1681/ASN.2011111130

DO - 10.1681/ASN.2011111130

M3 - Article

C2 - 22677553

VL - 23

SP - 1303

EP - 1308

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

SN - 1046-6673

IS - 8

ER -

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

Abstract

Keywords

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