TLR9 and TLR4 are required for the development of autoimmunity and lupus nephritis in pristane nephropathy

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Systemic lupus erythematosus is a common autoimmune disease, with kidney involvement a serious complication associated with poor prognosis. Humoral immune responses constitute the hallmark of disease, however T helper cells are required for the generation of autoantibodies, as well as the induction and progression of renal injury. Administration of pristane to genetically intact mice results in the development of hypergammaglobulinaemia with the production of lupus like autoantibodies and proliferative glomerulonephritis, with similarities to human lupus nephritis. TLRs are intricately linked to the development of autoimmunity and are involved in the development of lupus nephritis. We injected wild type, TLR9-/- and TLR4-/- mice with pristane and assessed cellular and humoral autoimmunity and renal injury, 8 months later. TLR9-/- mice demonstrated a predominant decrease in Th1 cytokine production which resulted in decreased anti-RNP antibody levels, while anti-dsDNA levels remained intact. Compared to wild type mice treated with pristane, functional and histological renal injury and glomerular immunoglobulin and complement deposition was decreased in TLR9-/- mice. TLR4-/- mice demonstrated a global decrease in both Th1, IFNgamma, and Th17 associated IL-17A and IL-6 cytokine production. Autoantibody levels of anti-dsDNA and anti-RNP were both decreased. Renal injury was attenuated in TLR4-/- mice which demonstrated less glomerular immunoglobulin and complement deposition. These results demonstrate that both TLR9 and TLR4 are required for full-blown autoimmunity and organ injury in experimental lupus induced by pristane.
Original languageEnglish
Pages (from-to)291 - 298
Number of pages8
JournalJournal of Autoimmunity
Volume35
Issue number4
DOIs
Publication statusPublished - 2010

Cite this

@article{48c0e81998784858952b1e6051aab4c4,
title = "TLR9 and TLR4 are required for the development of autoimmunity and lupus nephritis in pristane nephropathy",
abstract = "Systemic lupus erythematosus is a common autoimmune disease, with kidney involvement a serious complication associated with poor prognosis. Humoral immune responses constitute the hallmark of disease, however T helper cells are required for the generation of autoantibodies, as well as the induction and progression of renal injury. Administration of pristane to genetically intact mice results in the development of hypergammaglobulinaemia with the production of lupus like autoantibodies and proliferative glomerulonephritis, with similarities to human lupus nephritis. TLRs are intricately linked to the development of autoimmunity and are involved in the development of lupus nephritis. We injected wild type, TLR9-/- and TLR4-/- mice with pristane and assessed cellular and humoral autoimmunity and renal injury, 8 months later. TLR9-/- mice demonstrated a predominant decrease in Th1 cytokine production which resulted in decreased anti-RNP antibody levels, while anti-dsDNA levels remained intact. Compared to wild type mice treated with pristane, functional and histological renal injury and glomerular immunoglobulin and complement deposition was decreased in TLR9-/- mice. TLR4-/- mice demonstrated a global decrease in both Th1, IFNgamma, and Th17 associated IL-17A and IL-6 cytokine production. Autoantibody levels of anti-dsDNA and anti-RNP were both decreased. Renal injury was attenuated in TLR4-/- mice which demonstrated less glomerular immunoglobulin and complement deposition. These results demonstrate that both TLR9 and TLR4 are required for full-blown autoimmunity and organ injury in experimental lupus induced by pristane.",
author = "Summers, {Shaun Andrew} and Alberta Hoi and Oliver Steinmetz and Kim O'Sullivan and Joshua Ooi and Dragana Odobasic and Shizou Akira and Kitching, {Arthur Richard} and Holdsworth, {Stephen Roger}",
year = "2010",
doi = "10.1016/j.jaut.2010.05.004",
language = "English",
volume = "35",
pages = "291 -- 298",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Elsevier",
number = "4",

}

TLR9 and TLR4 are required for the development of autoimmunity and lupus nephritis in pristane nephropathy. / Summers, Shaun Andrew; Hoi, Alberta; Steinmetz, Oliver; O'Sullivan, Kim; Ooi, Joshua; Odobasic, Dragana; Akira, Shizou; Kitching, Arthur Richard; Holdsworth, Stephen Roger.

In: Journal of Autoimmunity, Vol. 35, No. 4, 2010, p. 291 - 298.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - TLR9 and TLR4 are required for the development of autoimmunity and lupus nephritis in pristane nephropathy

AU - Summers, Shaun Andrew

AU - Hoi, Alberta

AU - Steinmetz, Oliver

AU - O'Sullivan, Kim

AU - Ooi, Joshua

AU - Odobasic, Dragana

AU - Akira, Shizou

AU - Kitching, Arthur Richard

AU - Holdsworth, Stephen Roger

PY - 2010

Y1 - 2010

N2 - Systemic lupus erythematosus is a common autoimmune disease, with kidney involvement a serious complication associated with poor prognosis. Humoral immune responses constitute the hallmark of disease, however T helper cells are required for the generation of autoantibodies, as well as the induction and progression of renal injury. Administration of pristane to genetically intact mice results in the development of hypergammaglobulinaemia with the production of lupus like autoantibodies and proliferative glomerulonephritis, with similarities to human lupus nephritis. TLRs are intricately linked to the development of autoimmunity and are involved in the development of lupus nephritis. We injected wild type, TLR9-/- and TLR4-/- mice with pristane and assessed cellular and humoral autoimmunity and renal injury, 8 months later. TLR9-/- mice demonstrated a predominant decrease in Th1 cytokine production which resulted in decreased anti-RNP antibody levels, while anti-dsDNA levels remained intact. Compared to wild type mice treated with pristane, functional and histological renal injury and glomerular immunoglobulin and complement deposition was decreased in TLR9-/- mice. TLR4-/- mice demonstrated a global decrease in both Th1, IFNgamma, and Th17 associated IL-17A and IL-6 cytokine production. Autoantibody levels of anti-dsDNA and anti-RNP were both decreased. Renal injury was attenuated in TLR4-/- mice which demonstrated less glomerular immunoglobulin and complement deposition. These results demonstrate that both TLR9 and TLR4 are required for full-blown autoimmunity and organ injury in experimental lupus induced by pristane.

AB - Systemic lupus erythematosus is a common autoimmune disease, with kidney involvement a serious complication associated with poor prognosis. Humoral immune responses constitute the hallmark of disease, however T helper cells are required for the generation of autoantibodies, as well as the induction and progression of renal injury. Administration of pristane to genetically intact mice results in the development of hypergammaglobulinaemia with the production of lupus like autoantibodies and proliferative glomerulonephritis, with similarities to human lupus nephritis. TLRs are intricately linked to the development of autoimmunity and are involved in the development of lupus nephritis. We injected wild type, TLR9-/- and TLR4-/- mice with pristane and assessed cellular and humoral autoimmunity and renal injury, 8 months later. TLR9-/- mice demonstrated a predominant decrease in Th1 cytokine production which resulted in decreased anti-RNP antibody levels, while anti-dsDNA levels remained intact. Compared to wild type mice treated with pristane, functional and histological renal injury and glomerular immunoglobulin and complement deposition was decreased in TLR9-/- mice. TLR4-/- mice demonstrated a global decrease in both Th1, IFNgamma, and Th17 associated IL-17A and IL-6 cytokine production. Autoantibody levels of anti-dsDNA and anti-RNP were both decreased. Renal injury was attenuated in TLR4-/- mice which demonstrated less glomerular immunoglobulin and complement deposition. These results demonstrate that both TLR9 and TLR4 are required for full-blown autoimmunity and organ injury in experimental lupus induced by pristane.

U2 - 10.1016/j.jaut.2010.05.004

DO - 10.1016/j.jaut.2010.05.004

M3 - Article

VL - 35

SP - 291

EP - 298

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

IS - 4

ER -