Protection against autoimmune nephritis in MyD88-deficient MRL/lpr mice

Atsushi Sadanaga, Hitoshi Nakashima, Mitsuteru Akahoshi, Kohsuke Masutani, Katsuhisa Miyake, Takashi Igawa, Naonobu Sugiyama, Hiroaki Niiro, Mine Harada

研究成果: ジャーナルへの寄稿記事

87 引用 (Scopus)

抄録

Objective. To determine whether innate receptor signals play an important role in the development of autoimmune nephritis in MRL/lpr mice, an experimental model of lupus nephritis. Methods. MyD88 is a critical adaptor that is involved in signaling pathways through all of the Toll-like receptors (TLRs) except TLR-3. We therefore generated MyD88-knockout (MyD88-KO) MRL/lpr mice and examined them for histopathologic changes in the kidneys, cumulative survival rates, extent of lymphadenopathy and splenomegaly, serum chemistry, and immunologic parameters. In addition, to define the role of the MyD88-independent pathway in autoimmune nephritis, we injected MyD88-KO MRL/lpr mice intraperitoneally with either poly(I-C) (50 or 100 μg per mouse) or phosphate buffered saline and examined them for survival as well as for histopathologic, serologic, and immunologic parameters. Results. In comparison with wild-type mice, MyD88-KO MRL/lpr mice exhibited a prolonged lifespan, with no apparent development of autoimmune nephritis. Their kidneys showed no glomerular cell proliferation or crescent formation, along with a drastic decrease in the mesangial matrix. Lymphadenopathy and splenomegaly were less pronounced. Serum titers of anti-double-stranded DNA (anti-dsDNA) and production of cytokines, including interferon-α (IFNα), interleukln-12 (IL-12), IL-6, and IFNγ, in splenocytes were significantly reduced in MyD88-KO MRL/lpr mice. Interestingly, MyD88-KO MRL/lpr mice that had been treated with the MyD88-independent TLR-3 ligand poly(I-C) showed an almost complete reversion to the features of wild-type mice, demonstrating crescentic glomerulonephritis, with significant elevation of serum anti-dsDNA titers and increased cytokine production in splenocytes. Conclusion. The Findings indicate that both MyD88-dependent and MyD88-independent innate signals play a crucial role in the development of autoimmune nephritis in MRL/lpr mice.

元の言語英語
ページ(範囲)1618-1628
ページ数11
ジャーナルArthritis and rheumatism
56
発行部数5
DOI
出版物ステータス出版済み - 5 1 2007

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Inbred MRL lpr Mouse
Nephritis
Knockout Mice
Toll-Like Receptor 3
Splenomegaly
Interferons
Serum
Cytokines
Kidney
Lupus Nephritis
Toll-Like Receptors
Glomerulonephritis
Interleukin-6
Theoretical Models
Phosphates
Cell Proliferation
Ligands
DNA

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

これを引用

Sadanaga, A., Nakashima, H., Akahoshi, M., Masutani, K., Miyake, K., Igawa, T., ... Harada, M. (2007). Protection against autoimmune nephritis in MyD88-deficient MRL/lpr mice. Arthritis and rheumatism, 56(5), 1618-1628. https://doi.org/10.1002/art.22571

Protection against autoimmune nephritis in MyD88-deficient MRL/lpr mice. / Sadanaga, Atsushi; Nakashima, Hitoshi; Akahoshi, Mitsuteru; Masutani, Kohsuke; Miyake, Katsuhisa; Igawa, Takashi; Sugiyama, Naonobu; Niiro, Hiroaki; Harada, Mine.

:: Arthritis and rheumatism, 巻 56, 番号 5, 01.05.2007, p. 1618-1628.

研究成果: ジャーナルへの寄稿記事

Sadanaga, A, Nakashima, H, Akahoshi, M, Masutani, K, Miyake, K, Igawa, T, Sugiyama, N, Niiro, H & Harada, M 2007, 'Protection against autoimmune nephritis in MyD88-deficient MRL/lpr mice', Arthritis and rheumatism, 巻. 56, 番号 5, pp. 1618-1628. https://doi.org/10.1002/art.22571
Sadanaga A, Nakashima H, Akahoshi M, Masutani K, Miyake K, Igawa T その他. Protection against autoimmune nephritis in MyD88-deficient MRL/lpr mice. Arthritis and rheumatism. 2007 5 1;56(5):1618-1628. https://doi.org/10.1002/art.22571
Sadanaga, Atsushi ; Nakashima, Hitoshi ; Akahoshi, Mitsuteru ; Masutani, Kohsuke ; Miyake, Katsuhisa ; Igawa, Takashi ; Sugiyama, Naonobu ; Niiro, Hiroaki ; Harada, Mine. / Protection against autoimmune nephritis in MyD88-deficient MRL/lpr mice. :: Arthritis and rheumatism. 2007 ; 巻 56, 番号 5. pp. 1618-1628.
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abstract = "Objective. To determine whether innate receptor signals play an important role in the development of autoimmune nephritis in MRL/lpr mice, an experimental model of lupus nephritis. Methods. MyD88 is a critical adaptor that is involved in signaling pathways through all of the Toll-like receptors (TLRs) except TLR-3. We therefore generated MyD88-knockout (MyD88-KO) MRL/lpr mice and examined them for histopathologic changes in the kidneys, cumulative survival rates, extent of lymphadenopathy and splenomegaly, serum chemistry, and immunologic parameters. In addition, to define the role of the MyD88-independent pathway in autoimmune nephritis, we injected MyD88-KO MRL/lpr mice intraperitoneally with either poly(I-C) (50 or 100 μg per mouse) or phosphate buffered saline and examined them for survival as well as for histopathologic, serologic, and immunologic parameters. Results. In comparison with wild-type mice, MyD88-KO MRL/lpr mice exhibited a prolonged lifespan, with no apparent development of autoimmune nephritis. Their kidneys showed no glomerular cell proliferation or crescent formation, along with a drastic decrease in the mesangial matrix. Lymphadenopathy and splenomegaly were less pronounced. Serum titers of anti-double-stranded DNA (anti-dsDNA) and production of cytokines, including interferon-α (IFNα), interleukln-12 (IL-12), IL-6, and IFNγ, in splenocytes were significantly reduced in MyD88-KO MRL/lpr mice. Interestingly, MyD88-KO MRL/lpr mice that had been treated with the MyD88-independent TLR-3 ligand poly(I-C) showed an almost complete reversion to the features of wild-type mice, demonstrating crescentic glomerulonephritis, with significant elevation of serum anti-dsDNA titers and increased cytokine production in splenocytes. Conclusion. The Findings indicate that both MyD88-dependent and MyD88-independent innate signals play a crucial role in the development of autoimmune nephritis in MRL/lpr mice.",
author = "Atsushi Sadanaga and Hitoshi Nakashima and Mitsuteru Akahoshi and Kohsuke Masutani and Katsuhisa Miyake and Takashi Igawa and Naonobu Sugiyama and Hiroaki Niiro and Mine Harada",
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AU - Sadanaga, Atsushi

AU - Nakashima, Hitoshi

AU - Akahoshi, Mitsuteru

AU - Masutani, Kohsuke

AU - Miyake, Katsuhisa

AU - Igawa, Takashi

AU - Sugiyama, Naonobu

AU - Niiro, Hiroaki

AU - Harada, Mine

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N2 - Objective. To determine whether innate receptor signals play an important role in the development of autoimmune nephritis in MRL/lpr mice, an experimental model of lupus nephritis. Methods. MyD88 is a critical adaptor that is involved in signaling pathways through all of the Toll-like receptors (TLRs) except TLR-3. We therefore generated MyD88-knockout (MyD88-KO) MRL/lpr mice and examined them for histopathologic changes in the kidneys, cumulative survival rates, extent of lymphadenopathy and splenomegaly, serum chemistry, and immunologic parameters. In addition, to define the role of the MyD88-independent pathway in autoimmune nephritis, we injected MyD88-KO MRL/lpr mice intraperitoneally with either poly(I-C) (50 or 100 μg per mouse) or phosphate buffered saline and examined them for survival as well as for histopathologic, serologic, and immunologic parameters. Results. In comparison with wild-type mice, MyD88-KO MRL/lpr mice exhibited a prolonged lifespan, with no apparent development of autoimmune nephritis. Their kidneys showed no glomerular cell proliferation or crescent formation, along with a drastic decrease in the mesangial matrix. Lymphadenopathy and splenomegaly were less pronounced. Serum titers of anti-double-stranded DNA (anti-dsDNA) and production of cytokines, including interferon-α (IFNα), interleukln-12 (IL-12), IL-6, and IFNγ, in splenocytes were significantly reduced in MyD88-KO MRL/lpr mice. Interestingly, MyD88-KO MRL/lpr mice that had been treated with the MyD88-independent TLR-3 ligand poly(I-C) showed an almost complete reversion to the features of wild-type mice, demonstrating crescentic glomerulonephritis, with significant elevation of serum anti-dsDNA titers and increased cytokine production in splenocytes. Conclusion. The Findings indicate that both MyD88-dependent and MyD88-independent innate signals play a crucial role in the development of autoimmune nephritis in MRL/lpr mice.

AB - Objective. To determine whether innate receptor signals play an important role in the development of autoimmune nephritis in MRL/lpr mice, an experimental model of lupus nephritis. Methods. MyD88 is a critical adaptor that is involved in signaling pathways through all of the Toll-like receptors (TLRs) except TLR-3. We therefore generated MyD88-knockout (MyD88-KO) MRL/lpr mice and examined them for histopathologic changes in the kidneys, cumulative survival rates, extent of lymphadenopathy and splenomegaly, serum chemistry, and immunologic parameters. In addition, to define the role of the MyD88-independent pathway in autoimmune nephritis, we injected MyD88-KO MRL/lpr mice intraperitoneally with either poly(I-C) (50 or 100 μg per mouse) or phosphate buffered saline and examined them for survival as well as for histopathologic, serologic, and immunologic parameters. Results. In comparison with wild-type mice, MyD88-KO MRL/lpr mice exhibited a prolonged lifespan, with no apparent development of autoimmune nephritis. Their kidneys showed no glomerular cell proliferation or crescent formation, along with a drastic decrease in the mesangial matrix. Lymphadenopathy and splenomegaly were less pronounced. Serum titers of anti-double-stranded DNA (anti-dsDNA) and production of cytokines, including interferon-α (IFNα), interleukln-12 (IL-12), IL-6, and IFNγ, in splenocytes were significantly reduced in MyD88-KO MRL/lpr mice. Interestingly, MyD88-KO MRL/lpr mice that had been treated with the MyD88-independent TLR-3 ligand poly(I-C) showed an almost complete reversion to the features of wild-type mice, demonstrating crescentic glomerulonephritis, with significant elevation of serum anti-dsDNA titers and increased cytokine production in splenocytes. Conclusion. The Findings indicate that both MyD88-dependent and MyD88-independent innate signals play a crucial role in the development of autoimmune nephritis in MRL/lpr mice.

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