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The Th17-defining transcription factor RORγt promotes glomerulonephritis

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The Th17-defining transcription factor RORγt promotes glomerulonephritis. / Steinmetz, Oliver M; Summers, Shaun A; Gan, Poh-Yi; Semple, Timothy; Holdsworth, Stephen R; Kitching, A Richard.

In: J AM SOC NEPHROL, Vol. 22, No. 3, 03.2011, p. 472-83.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Steinmetz, OM, Summers, SA, Gan, P-Y, Semple, T, Holdsworth, SR & Kitching, AR 2011, 'The Th17-defining transcription factor RORγt promotes glomerulonephritis', J AM SOC NEPHROL, vol. 22, no. 3, pp. 472-83. https://doi.org/10.1681/ASN.2010040435

APA

Steinmetz, O. M., Summers, S. A., Gan, P-Y., Semple, T., Holdsworth, S. R., & Kitching, A. R. (2011). The Th17-defining transcription factor RORγt promotes glomerulonephritis. J AM SOC NEPHROL, 22(3), 472-83. https://doi.org/10.1681/ASN.2010040435

Vancouver

Steinmetz OM, Summers SA, Gan P-Y, Semple T, Holdsworth SR, Kitching AR. The Th17-defining transcription factor RORγt promotes glomerulonephritis. J AM SOC NEPHROL. 2011 Mar;22(3):472-83. https://doi.org/10.1681/ASN.2010040435

Bibtex

@article{80d7e20a42a442e7b59e3245b96a4804,
title = "The Th17-defining transcription factor RORγt promotes glomerulonephritis",
abstract = "Although Th17 responses may contribute to the pathogenesis of glomerulonephritis, whether the key transcription factor in Th17 cell development, RORγt, also promotes glomerulonephritis is unknown. Here, we induced crescentic glomerulonephritis in wild-type and RORγt-deficient (RORγt(-/-)) mice. RORγt(-/-) mice were protected from disease, with reduced histologic and functional injury and decreased leukocyte infiltration. Because RORγt(-/-) mice lack lymph nodes, which may influence the development of nephritis, we performed cell-transfer studies. We reconstituted Rag1(-/-) mice, which lack adaptive immunity but otherwise have normal architecture of the lymphatic system, with splenocytes from na{\"i}ve wild-type or RORγt(-/-) mice. Mice receiving wild-type splenocytes exhibited high mortality from renal failure after induction of nephritis whereas mice receiving RORγt(-/-) cells were protected. To determine the effect of RORγt deficiency specifically in T helper cells, we isolated na{\"i}ve CD4(+) T cells from wild-type and RORγt(-/-) mice and transferred them into Rag1(-/-) animals. Recipients of wild-type CD4(+) T cells developed severe glomerulonephritis whereas recipients of RORγt(-/-) cells developed less severe disease. To exclude effects of altered regulatory T cell (Treg) development caused by RORγt deficiency, we transferred na{\"i}ve CD4(+) T cells depleted of Tregs into Rag1(-/-) mice. Recipients of wild-type, Treg-depleted, CD4(+) T cells developed severe glomerulonephritis whereas recipients of RORγt(-/-), Treg-depleted CD4(+) T cells did not. Taken together, this study demonstrates that RORγt promotes the development of crescentic glomerulonephritis by directing nephritogenic Th17 responses.",
keywords = "Adaptive Immunity, Adoptive Transfer, Animals, CD4-Positive T-Lymphocytes, Disease Models, Animal, Female, Glomerulonephritis, Homeodomain Proteins, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Nuclear Receptor Subfamily 1, Group F, Member 3, T-Lymphocytes, Regulatory, Th1 Cells, Th17 Cells",
author = "Steinmetz, {Oliver M} and Summers, {Shaun A} and Poh-Yi Gan and Timothy Semple and Holdsworth, {Stephen R} and Kitching, {A Richard}",
year = "2011",
month = mar,
doi = "10.1681/ASN.2010040435",
language = "English",
volume = "22",
pages = "472--83",
journal = "J AM SOC NEPHROL",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "3",

}

RIS

TY - JOUR

T1 - The Th17-defining transcription factor RORγt promotes glomerulonephritis

AU - Steinmetz, Oliver M

AU - Summers, Shaun A

AU - Gan, Poh-Yi

AU - Semple, Timothy

AU - Holdsworth, Stephen R

AU - Kitching, A Richard

PY - 2011/3

Y1 - 2011/3

N2 - Although Th17 responses may contribute to the pathogenesis of glomerulonephritis, whether the key transcription factor in Th17 cell development, RORγt, also promotes glomerulonephritis is unknown. Here, we induced crescentic glomerulonephritis in wild-type and RORγt-deficient (RORγt(-/-)) mice. RORγt(-/-) mice were protected from disease, with reduced histologic and functional injury and decreased leukocyte infiltration. Because RORγt(-/-) mice lack lymph nodes, which may influence the development of nephritis, we performed cell-transfer studies. We reconstituted Rag1(-/-) mice, which lack adaptive immunity but otherwise have normal architecture of the lymphatic system, with splenocytes from naïve wild-type or RORγt(-/-) mice. Mice receiving wild-type splenocytes exhibited high mortality from renal failure after induction of nephritis whereas mice receiving RORγt(-/-) cells were protected. To determine the effect of RORγt deficiency specifically in T helper cells, we isolated naïve CD4(+) T cells from wild-type and RORγt(-/-) mice and transferred them into Rag1(-/-) animals. Recipients of wild-type CD4(+) T cells developed severe glomerulonephritis whereas recipients of RORγt(-/-) cells developed less severe disease. To exclude effects of altered regulatory T cell (Treg) development caused by RORγt deficiency, we transferred naïve CD4(+) T cells depleted of Tregs into Rag1(-/-) mice. Recipients of wild-type, Treg-depleted, CD4(+) T cells developed severe glomerulonephritis whereas recipients of RORγt(-/-), Treg-depleted CD4(+) T cells did not. Taken together, this study demonstrates that RORγt promotes the development of crescentic glomerulonephritis by directing nephritogenic Th17 responses.

AB - Although Th17 responses may contribute to the pathogenesis of glomerulonephritis, whether the key transcription factor in Th17 cell development, RORγt, also promotes glomerulonephritis is unknown. Here, we induced crescentic glomerulonephritis in wild-type and RORγt-deficient (RORγt(-/-)) mice. RORγt(-/-) mice were protected from disease, with reduced histologic and functional injury and decreased leukocyte infiltration. Because RORγt(-/-) mice lack lymph nodes, which may influence the development of nephritis, we performed cell-transfer studies. We reconstituted Rag1(-/-) mice, which lack adaptive immunity but otherwise have normal architecture of the lymphatic system, with splenocytes from naïve wild-type or RORγt(-/-) mice. Mice receiving wild-type splenocytes exhibited high mortality from renal failure after induction of nephritis whereas mice receiving RORγt(-/-) cells were protected. To determine the effect of RORγt deficiency specifically in T helper cells, we isolated naïve CD4(+) T cells from wild-type and RORγt(-/-) mice and transferred them into Rag1(-/-) animals. Recipients of wild-type CD4(+) T cells developed severe glomerulonephritis whereas recipients of RORγt(-/-) cells developed less severe disease. To exclude effects of altered regulatory T cell (Treg) development caused by RORγt deficiency, we transferred naïve CD4(+) T cells depleted of Tregs into Rag1(-/-) mice. Recipients of wild-type, Treg-depleted, CD4(+) T cells developed severe glomerulonephritis whereas recipients of RORγt(-/-), Treg-depleted CD4(+) T cells did not. Taken together, this study demonstrates that RORγt promotes the development of crescentic glomerulonephritis by directing nephritogenic Th17 responses.

KW - Adaptive Immunity

KW - Adoptive Transfer

KW - Animals

KW - CD4-Positive T-Lymphocytes

KW - Disease Models, Animal

KW - Female

KW - Glomerulonephritis

KW - Homeodomain Proteins

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Nuclear Receptor Subfamily 1, Group F, Member 3

KW - T-Lymphocytes, Regulatory

KW - Th1 Cells

KW - Th17 Cells

U2 - 10.1681/ASN.2010040435

DO - 10.1681/ASN.2010040435

M3 - SCORING: Journal article

C2 - 21183590

VL - 22

SP - 472

EP - 483

JO - J AM SOC NEPHROL

JF - J AM SOC NEPHROL

SN - 1046-6673

IS - 3

ER -