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IRF4 deficiency abrogates lupus nephritis despite enhancing systemic cytokine production.

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IRF4 deficiency abrogates lupus nephritis despite enhancing systemic cytokine production. / Lech, Maciej; Weidenbusch, Marc; Kulkarni, Onkar P; Ryu, Mi; Darisipudi, Murthy Narayana; Susanti, Heni Eka; Mittrücker, Hans Willi; Mak, Tak W; Anders, Hans-Joachim.

in: J AM SOC NEPHROL, Jahrgang 22, Nr. 8, 8, 2011, S. 1443-1452.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Lech, M, Weidenbusch, M, Kulkarni, OP, Ryu, M, Darisipudi, MN, Susanti, HE, Mittrücker, HW, Mak, TW & Anders, H-J 2011, 'IRF4 deficiency abrogates lupus nephritis despite enhancing systemic cytokine production.', J AM SOC NEPHROL, Jg. 22, Nr. 8, 8, S. 1443-1452. <http://www.ncbi.nlm.nih.gov/pubmed/21742731?dopt=Citation>

APA

Lech, M., Weidenbusch, M., Kulkarni, O. P., Ryu, M., Darisipudi, M. N., Susanti, H. E., Mittrücker, H. W., Mak, T. W., & Anders, H-J. (2011). IRF4 deficiency abrogates lupus nephritis despite enhancing systemic cytokine production. J AM SOC NEPHROL, 22(8), 1443-1452. [8]. http://www.ncbi.nlm.nih.gov/pubmed/21742731?dopt=Citation

Vancouver

Lech M, Weidenbusch M, Kulkarni OP, Ryu M, Darisipudi MN, Susanti HE et al. IRF4 deficiency abrogates lupus nephritis despite enhancing systemic cytokine production. J AM SOC NEPHROL. 2011;22(8):1443-1452. 8.

Bibtex

@article{f7841c12f0cd47748badaddb961538d5,
title = "IRF4 deficiency abrogates lupus nephritis despite enhancing systemic cytokine production.",
abstract = "The IFN-regulatory factors IRF1, IRF3, IRF5, and IRF7 modulate processes involved in the pathogenesis of systemic lupus and lupus nephritis, but the contribution of IRF4, which has multiple roles in innate and adaptive immunity, is unknown. To determine a putative pathogenic role of IRF4 in lupus, we crossed Irf4-deficient mice with autoimmune C57BL/6-(Fas)lpr mice. IRF4 deficiency associated with increased activation of antigen-presenting cells in C57BL/6-(Fas)lpr mice, resulting in a massive increase in plasma levels of TNF and IL-12p40, suggesting that IRF4 suppresses cytokine release in these mice. Nevertheless, IRF4 deficiency completely protected these mice from glomerulonephritis and lung disease. The mice were hypogammaglobulinemic and lacked antinuclear and anti-dsDNA autoantibodies, revealing the requirement of IRF4 for the maturation of plasma cells. As a consequence, Irf4-deficient C57BL/6-(Fas)lpr mice neither developed immune complex disease nor glomerular activation of complement. In addition, lack of IRF4 impaired the maturation of Th17 effector T cells and reduced plasma levels of IL-17 and IL-21, which are cytokines known to contribute to autoimmune tissue injury. In summary, IRF4 deficiency enhances systemic inflammation and the activation of antigen-presenting cells but also prevents the maturation of plasma cells and effector T cells. Because these adaptive immune effectors are essential for the evolution of lupus nephritis, we conclude that IRF4 promotes the development of lupus nephritis despite suppressing antigen-presenting cells.",
keywords = "Animals, Female, Genotype, Mice, Mice, Inbred C57BL, Models, Biological, Mice, Transgenic, Immunity, Innate, Cytokines/metabolism, Macrophages/metabolism, Autoimmune Diseases/pathology, Interferon Regulatory Factors/*genetics, Kidney/pathology, Lupus Nephritis/*genetics/*metabolism, Th17 Cells/metabolism, Animals, Female, Genotype, Mice, Mice, Inbred C57BL, Models, Biological, Mice, Transgenic, Immunity, Innate, Cytokines/metabolism, Macrophages/metabolism, Autoimmune Diseases/pathology, Interferon Regulatory Factors/*genetics, Kidney/pathology, Lupus Nephritis/*genetics/*metabolism, Th17 Cells/metabolism",
author = "Maciej Lech and Marc Weidenbusch and Kulkarni, {Onkar P} and Mi Ryu and Darisipudi, {Murthy Narayana} and Susanti, {Heni Eka} and Mittr{\"u}cker, {Hans Willi} and Mak, {Tak W} and Hans-Joachim Anders",
year = "2011",
language = "English",
volume = "22",
pages = "1443--1452",
journal = "J AM SOC NEPHROL",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "8",

}

RIS

TY - JOUR

T1 - IRF4 deficiency abrogates lupus nephritis despite enhancing systemic cytokine production.

AU - Lech, Maciej

AU - Weidenbusch, Marc

AU - Kulkarni, Onkar P

AU - Ryu, Mi

AU - Darisipudi, Murthy Narayana

AU - Susanti, Heni Eka

AU - Mittrücker, Hans Willi

AU - Mak, Tak W

AU - Anders, Hans-Joachim

PY - 2011

Y1 - 2011

N2 - The IFN-regulatory factors IRF1, IRF3, IRF5, and IRF7 modulate processes involved in the pathogenesis of systemic lupus and lupus nephritis, but the contribution of IRF4, which has multiple roles in innate and adaptive immunity, is unknown. To determine a putative pathogenic role of IRF4 in lupus, we crossed Irf4-deficient mice with autoimmune C57BL/6-(Fas)lpr mice. IRF4 deficiency associated with increased activation of antigen-presenting cells in C57BL/6-(Fas)lpr mice, resulting in a massive increase in plasma levels of TNF and IL-12p40, suggesting that IRF4 suppresses cytokine release in these mice. Nevertheless, IRF4 deficiency completely protected these mice from glomerulonephritis and lung disease. The mice were hypogammaglobulinemic and lacked antinuclear and anti-dsDNA autoantibodies, revealing the requirement of IRF4 for the maturation of plasma cells. As a consequence, Irf4-deficient C57BL/6-(Fas)lpr mice neither developed immune complex disease nor glomerular activation of complement. In addition, lack of IRF4 impaired the maturation of Th17 effector T cells and reduced plasma levels of IL-17 and IL-21, which are cytokines known to contribute to autoimmune tissue injury. In summary, IRF4 deficiency enhances systemic inflammation and the activation of antigen-presenting cells but also prevents the maturation of plasma cells and effector T cells. Because these adaptive immune effectors are essential for the evolution of lupus nephritis, we conclude that IRF4 promotes the development of lupus nephritis despite suppressing antigen-presenting cells.

AB - The IFN-regulatory factors IRF1, IRF3, IRF5, and IRF7 modulate processes involved in the pathogenesis of systemic lupus and lupus nephritis, but the contribution of IRF4, which has multiple roles in innate and adaptive immunity, is unknown. To determine a putative pathogenic role of IRF4 in lupus, we crossed Irf4-deficient mice with autoimmune C57BL/6-(Fas)lpr mice. IRF4 deficiency associated with increased activation of antigen-presenting cells in C57BL/6-(Fas)lpr mice, resulting in a massive increase in plasma levels of TNF and IL-12p40, suggesting that IRF4 suppresses cytokine release in these mice. Nevertheless, IRF4 deficiency completely protected these mice from glomerulonephritis and lung disease. The mice were hypogammaglobulinemic and lacked antinuclear and anti-dsDNA autoantibodies, revealing the requirement of IRF4 for the maturation of plasma cells. As a consequence, Irf4-deficient C57BL/6-(Fas)lpr mice neither developed immune complex disease nor glomerular activation of complement. In addition, lack of IRF4 impaired the maturation of Th17 effector T cells and reduced plasma levels of IL-17 and IL-21, which are cytokines known to contribute to autoimmune tissue injury. In summary, IRF4 deficiency enhances systemic inflammation and the activation of antigen-presenting cells but also prevents the maturation of plasma cells and effector T cells. Because these adaptive immune effectors are essential for the evolution of lupus nephritis, we conclude that IRF4 promotes the development of lupus nephritis despite suppressing antigen-presenting cells.

KW - Animals

KW - Female

KW - Genotype

KW - Mice

KW - Mice, Inbred C57BL

KW - Models, Biological

KW - Mice, Transgenic

KW - Immunity, Innate

KW - Cytokines/metabolism

KW - Macrophages/metabolism

KW - Autoimmune Diseases/pathology

KW - Interferon Regulatory Factors/genetics

KW - Kidney/pathology

KW - Lupus Nephritis/genetics/metabolism

KW - Th17 Cells/metabolism

KW - Animals

KW - Female

KW - Genotype

KW - Mice

KW - Mice, Inbred C57BL

KW - Models, Biological

KW - Mice, Transgenic

KW - Immunity, Innate

KW - Cytokines/metabolism

KW - Macrophages/metabolism

KW - Autoimmune Diseases/pathology

KW - Interferon Regulatory Factors/genetics

KW - Kidney/pathology

KW - Lupus Nephritis/genetics/metabolism

KW - Th17 Cells/metabolism

M3 - SCORING: Journal article

VL - 22

SP - 1443

EP - 1452

JO - J AM SOC NEPHROL

JF - J AM SOC NEPHROL

SN - 1046-6673

IS - 8

M1 - 8

ER -