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Auricular chondritis in NOD.DQ8.Aβo (Ag7–/–) transgenic mice resembles human relapsing polychondritis
Veena Taneja, … , Harvinder S. Luthra, Chella S. David
Veena Taneja, … , Harvinder S. Luthra, Chella S. David
Published December 15, 2003
Citation Information: J Clin Invest. 2003;112(12):1843-1850. https://doi.org/10.1172/JCI17450.
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Article Autoimmunity

Auricular chondritis in NOD.DQ8.Aβo (Ag7–/–) transgenic mice resembles human relapsing polychondritis

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Abstract

Relapsing polychondritis is a multisystem autoimmune disease involving cartilage destruction but no known causative antigen. HLA-DQ8 has been associated with various autoimmune diseases in humans. To study the role of DQ8 in autoimmune diseases, we have generated transgenic mice expressing DQ8 (DQA1*0301, DQB1*0302) in a NOD background lacking endogenous class II molecules (Aβo). Upon immunization with type II collagen (CII), 85% of NOD.DQ8 mice develop severe experimental polychondritis, auricular chondritis, and polyarthritis, with clinical and histological similarities to relapsing polychondritis (RP) in humans. CII-immunized mice mount a T cell response and produce Ab’s to type IX collagen (CIX) and self-CII. Transgene-negative littermates do not develop any serological and clinical manifestations following immunization. B10.DQ8 transgenic mice develop polyarthritis and Ab’s to CII only. The susceptibility to auricular chondritis in NOD.DQ8 mice can be attributed to response to CIX. A higher number of activated cells, CD4+CD44hiCD62Llo, and lower regulatory cells CD4+CD152+CD25+ were observed in NOD.DQ8 mice compared with B10.DQ8 mice. The NOD.DQ8 mice provide a model of RP with a high disease incidence and multiple organ involvement to investigate putative autoantigen and regulatory cells involved in disease pathogenesis. An experimental model restricted by the human class II molecule will be valuable when studying the role of various collagens in immunologic and pathologic responses in human RP.

Authors

Veena Taneja, Marie Griffiths, Marshall Behrens, Harvinder S. Luthra, Chella S. David

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Figure 1

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Swelling and edema with a shrunken ear as observed in a human ear (a) an...
Swelling and edema with a shrunken ear as observed in a human ear (a) and an affected mouse (b) with auricular chondritis. H&E-stained section of a normal (c) and a chondritic ear (d) of NOD.DQ8 transgenic mice showing massive infiltration of cells in the chondritic ear. Toludine blue staining of a normal ear (e) and a chondritic ear (f) showing destruction of cartilage in the latter, with residual cartilage seen among infiltrates as shown within the boxed area (magnification ×200). Micrographs are ×50 magnification.
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