Toll-like receptor 2 induces Th17 myeloperoxidase autoimmunity while Toll-like receptor 9 drives Th1 autoimmunity in murine vasculitis

Shaun Andrew Summers, Oliver Steinmetz, Poh-Yi Gan, Joshua Ooi, Dragana Odobasic, Arthur Kitching, Stephen Holdsworth

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Autoantibodies constitute the hallmark of antineutrophil cytoplasmic antibody-associated vasculitis (AAV); however, CD4+ T cells play an essential role in the development of autoimmunity. Infection is associated with vasculitis, with Toll-like receptors (TLRs) a potential link between infection and autoimmunity. This study was undertaken to investigate the role of TLR ligation on cellular and humoral autoimmunity and glomerular injury in experimental myeloperoxidase (MPO)-induced AAV. METHODS: We analyzed autoimmune responses in wild-type mice immunized with MPO alone or coimmunized with MPO and a TLR-2 or TLR-9 ligand. The major vascular injury found in human disease, glomerulonephritis with focal necrosis, was triggered by administering a subnephritogenic dose of nephrotoxic serum.
Original languageEnglish
Pages (from-to)1124 - 1135
Number of pages12
JournalArthritis and Rheumatism
Volume63
Issue number4
DOIs
Publication statusPublished - 2011

Cite this

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title = "Toll-like receptor 2 induces Th17 myeloperoxidase autoimmunity while Toll-like receptor 9 drives Th1 autoimmunity in murine vasculitis",
abstract = "Autoantibodies constitute the hallmark of antineutrophil cytoplasmic antibody-associated vasculitis (AAV); however, CD4+ T cells play an essential role in the development of autoimmunity. Infection is associated with vasculitis, with Toll-like receptors (TLRs) a potential link between infection and autoimmunity. This study was undertaken to investigate the role of TLR ligation on cellular and humoral autoimmunity and glomerular injury in experimental myeloperoxidase (MPO)-induced AAV. METHODS: We analyzed autoimmune responses in wild-type mice immunized with MPO alone or coimmunized with MPO and a TLR-2 or TLR-9 ligand. The major vascular injury found in human disease, glomerulonephritis with focal necrosis, was triggered by administering a subnephritogenic dose of nephrotoxic serum.",
author = "Summers, {Shaun Andrew} and Oliver Steinmetz and Poh-Yi Gan and Joshua Ooi and Dragana Odobasic and Arthur Kitching and Stephen Holdsworth",
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Toll-like receptor 2 induces Th17 myeloperoxidase autoimmunity while Toll-like receptor 9 drives Th1 autoimmunity in murine vasculitis. / Summers, Shaun Andrew; Steinmetz, Oliver; Gan, Poh-Yi; Ooi, Joshua; Odobasic, Dragana; Kitching, Arthur; Holdsworth, Stephen.

In: Arthritis and Rheumatism, Vol. 63, No. 4, 2011, p. 1124 - 1135.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Toll-like receptor 2 induces Th17 myeloperoxidase autoimmunity while Toll-like receptor 9 drives Th1 autoimmunity in murine vasculitis

AU - Summers, Shaun Andrew

AU - Steinmetz, Oliver

AU - Gan, Poh-Yi

AU - Ooi, Joshua

AU - Odobasic, Dragana

AU - Kitching, Arthur

AU - Holdsworth, Stephen

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AB - Autoantibodies constitute the hallmark of antineutrophil cytoplasmic antibody-associated vasculitis (AAV); however, CD4+ T cells play an essential role in the development of autoimmunity. Infection is associated with vasculitis, with Toll-like receptors (TLRs) a potential link between infection and autoimmunity. This study was undertaken to investigate the role of TLR ligation on cellular and humoral autoimmunity and glomerular injury in experimental myeloperoxidase (MPO)-induced AAV. METHODS: We analyzed autoimmune responses in wild-type mice immunized with MPO alone or coimmunized with MPO and a TLR-2 or TLR-9 ligand. The major vascular injury found in human disease, glomerulonephritis with focal necrosis, was triggered by administering a subnephritogenic dose of nephrotoxic serum.

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