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

doi:10.1002/art.30208

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 journal › Article › Research › peer-review

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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 language	English
Pages (from-to)	1124 - 1135
Number of pages	12
Journal	Arthritis and Rheumatism
Volume	63
Issue number	4
DOIs	https://doi.org/10.1002/art.30208
Publication status	Published - 2011

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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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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

PY - 2011

Y1 - 2011

N2 - 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.

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.

UR - http://onlinelibrary.wiley.com/doi/10.1002/art.30208/pdf

U2 - 10.1002/art.30208

DO - 10.1002/art.30208

M3 - Article

VL - 63

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EP - 1135

JO - Arthritis & Rheumatology

JF - Arthritis & Rheumatology

SN - 2326-5191

IS - 4

ER -

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

Abstract

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