Interleukin-17A promotes early but attenuates established disease in crescentic glomerulonephritis in mice

Dragana Odobasic, Poh-Yi Gan, Shaun Andrew Summers, Timothy Semple, Ruth Muljadi, Yoichiro Iwakura, Arthur Kitching, Stephen Holdsworth

Research output: Contribution to journalArticleResearchpeer-review

Abstract

T helper (Th)17 cells might contribute to immune-mediated renal injury. Thus, we sought to define the time course of IL-17A-induced kidney damage and examined the relation between Th17 and Th1 cells in a model of crescentic anti-glomerular basement membrane glomerulonephritis. Renal injury and immune responses were assessed in wild-type and in IL-17A-deficient mice on days 6, 14, and 21 of disease development. On day 6, when mild glomerulonephritis developed, IL-17A-deficient mice were protected from renal injury. On day 14, when more severe disease developed, protection from renal injury due to IL-17A deficiency was less evident. On day 21, when crescentic glomerulonephritis was fully established, disease was enhanced in IL-17A(-/-) mice, with increased glomerular T-cell accumulation and fibrin deposition, and augmented Th1 responses. Mice lacking the Th17-promoting cytokine, IL-23 (p19), also developed more severe disease than wild-type animals on day 21. In contrast, mice deficient in the key Th1-promoting cytokine, IL-12 (p35), had decreased Th1 and increased Th17 responses and developed less severe crescentic glomerulonephritis than wild-type animals. These studies show that IL-17A contributes to early glomerular injury, but it attenuates established crescentic glomerulonephritis by suppressing Th1 responses. They provide further evidence that Th1 cells mediate crescentic injury in this model and that Th1 and Th17 cells counterregulate each other during disease development.
Original languageEnglish
Pages (from-to)1188 - 1198
Number of pages11
JournalAmerican Journal of Pathology
Volume179
Issue number3
DOIs
Publication statusPublished - 2011

Cite this

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title = "Interleukin-17A promotes early but attenuates established disease in crescentic glomerulonephritis in mice",
abstract = "T helper (Th)17 cells might contribute to immune-mediated renal injury. Thus, we sought to define the time course of IL-17A-induced kidney damage and examined the relation between Th17 and Th1 cells in a model of crescentic anti-glomerular basement membrane glomerulonephritis. Renal injury and immune responses were assessed in wild-type and in IL-17A-deficient mice on days 6, 14, and 21 of disease development. On day 6, when mild glomerulonephritis developed, IL-17A-deficient mice were protected from renal injury. On day 14, when more severe disease developed, protection from renal injury due to IL-17A deficiency was less evident. On day 21, when crescentic glomerulonephritis was fully established, disease was enhanced in IL-17A(-/-) mice, with increased glomerular T-cell accumulation and fibrin deposition, and augmented Th1 responses. Mice lacking the Th17-promoting cytokine, IL-23 (p19), also developed more severe disease than wild-type animals on day 21. In contrast, mice deficient in the key Th1-promoting cytokine, IL-12 (p35), had decreased Th1 and increased Th17 responses and developed less severe crescentic glomerulonephritis than wild-type animals. These studies show that IL-17A contributes to early glomerular injury, but it attenuates established crescentic glomerulonephritis by suppressing Th1 responses. They provide further evidence that Th1 cells mediate crescentic injury in this model and that Th1 and Th17 cells counterregulate each other during disease development.",
author = "Dragana Odobasic and Poh-Yi Gan and Summers, {Shaun Andrew} and Timothy Semple and Ruth Muljadi and Yoichiro Iwakura and Arthur Kitching and Stephen Holdsworth",
year = "2011",
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language = "English",
volume = "179",
pages = "1188 -- 1198",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "American Society for Investigative Pathology",
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}

Interleukin-17A promotes early but attenuates established disease in crescentic glomerulonephritis in mice. / Odobasic, Dragana; Gan, Poh-Yi; Summers, Shaun Andrew; Semple, Timothy; Muljadi, Ruth; Iwakura, Yoichiro; Kitching, Arthur; Holdsworth, Stephen.

In: American Journal of Pathology, Vol. 179, No. 3, 2011, p. 1188 - 1198.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Interleukin-17A promotes early but attenuates established disease in crescentic glomerulonephritis in mice

AU - Odobasic, Dragana

AU - Gan, Poh-Yi

AU - Summers, Shaun Andrew

AU - Semple, Timothy

AU - Muljadi, Ruth

AU - Iwakura, Yoichiro

AU - Kitching, Arthur

AU - Holdsworth, Stephen

PY - 2011

Y1 - 2011

N2 - T helper (Th)17 cells might contribute to immune-mediated renal injury. Thus, we sought to define the time course of IL-17A-induced kidney damage and examined the relation between Th17 and Th1 cells in a model of crescentic anti-glomerular basement membrane glomerulonephritis. Renal injury and immune responses were assessed in wild-type and in IL-17A-deficient mice on days 6, 14, and 21 of disease development. On day 6, when mild glomerulonephritis developed, IL-17A-deficient mice were protected from renal injury. On day 14, when more severe disease developed, protection from renal injury due to IL-17A deficiency was less evident. On day 21, when crescentic glomerulonephritis was fully established, disease was enhanced in IL-17A(-/-) mice, with increased glomerular T-cell accumulation and fibrin deposition, and augmented Th1 responses. Mice lacking the Th17-promoting cytokine, IL-23 (p19), also developed more severe disease than wild-type animals on day 21. In contrast, mice deficient in the key Th1-promoting cytokine, IL-12 (p35), had decreased Th1 and increased Th17 responses and developed less severe crescentic glomerulonephritis than wild-type animals. These studies show that IL-17A contributes to early glomerular injury, but it attenuates established crescentic glomerulonephritis by suppressing Th1 responses. They provide further evidence that Th1 cells mediate crescentic injury in this model and that Th1 and Th17 cells counterregulate each other during disease development.

AB - T helper (Th)17 cells might contribute to immune-mediated renal injury. Thus, we sought to define the time course of IL-17A-induced kidney damage and examined the relation between Th17 and Th1 cells in a model of crescentic anti-glomerular basement membrane glomerulonephritis. Renal injury and immune responses were assessed in wild-type and in IL-17A-deficient mice on days 6, 14, and 21 of disease development. On day 6, when mild glomerulonephritis developed, IL-17A-deficient mice were protected from renal injury. On day 14, when more severe disease developed, protection from renal injury due to IL-17A deficiency was less evident. On day 21, when crescentic glomerulonephritis was fully established, disease was enhanced in IL-17A(-/-) mice, with increased glomerular T-cell accumulation and fibrin deposition, and augmented Th1 responses. Mice lacking the Th17-promoting cytokine, IL-23 (p19), also developed more severe disease than wild-type animals on day 21. In contrast, mice deficient in the key Th1-promoting cytokine, IL-12 (p35), had decreased Th1 and increased Th17 responses and developed less severe crescentic glomerulonephritis than wild-type animals. These studies show that IL-17A contributes to early glomerular injury, but it attenuates established crescentic glomerulonephritis by suppressing Th1 responses. They provide further evidence that Th1 cells mediate crescentic injury in this model and that Th1 and Th17 cells counterregulate each other during disease development.

UR - http://www.ncbi.nlm.nih.gov/pubmed/21741931

U2 - 10.1016/j.ajpath.2011.05.039

DO - 10.1016/j.ajpath.2011.05.039

M3 - Article

VL - 179

SP - 1188

EP - 1198

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 3

ER -