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http://purl.uniprot.org/citations/16453294http://www.w3.org/2000/01/rdf-schema#comment"

Objective

To test whether immunizing mice with autoantigens closely linked to mixed connective tissue disease (MCTD) could induce an MCTD-like clinical syndrome distinguishable from systemic lupus erythematosus (SLE).

Methods

Transgenic and knockout C57BL/6-derived mice were immunized subcutaneously at age 8-12 weeks with U1-70-kd small nuclear RNP (70K) fusion protein along with either Freund's complete adjuvant (CFA) or U1 RNA. After 2 months, mice were killed and analyzed histologically and serologically.

Results

Immunization of C57BL/6-derived mice transgenic for human HLA-DR4 with 70K and either CFA or U1 RNA led to anti-70K antibodies in 62% of mice (21 of 34), and diversified anti-RNP immune responses. MCTD-like lung disease also developed in 50% of immunized mice (17 of 34), and anti-70K antibodies were strongly correlated with lung disease. CFA and U1 RNA were comparably able to induce this syndrome. Mice deficient in Toll-like receptor 3 (TLR-3) also developed this same syndrome when immunized with 70K and CFA. However, TLR-3(-/-) mice failed to develop MCTD-like lung disease when treated with 70K and U1 RNA. Rather, TLR-3(-/-) mice immunized with 70K and U1 RNA developed an autoimmune syndrome characterized by glomerulonephritis typical of SLE.

Conclusion

Exposure to 70K in an appropriate context is sufficient to induce autoimmunity and target organ injury consistent with MCTD. This system represents a new model of autoimmune interstitial lung disease, and establishes a closer link between anti-70K immunity and MCTD-like lung disease. Of note, changes in innate immune signaling can cause the same trigger to lead to the development of SLE-like nephritis rather than MCTD-like lung disease."xsd:string
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http://purl.uniprot.org/citations/16453294http://purl.uniprot.org/core/author"Barber G.N."xsd:string
http://purl.uniprot.org/citations/16453294http://purl.uniprot.org/core/author"Zang Y."xsd:string
http://purl.uniprot.org/citations/16453294http://purl.uniprot.org/core/author"Nassiri M."xsd:string
http://purl.uniprot.org/citations/16453294http://purl.uniprot.org/core/author"Hoffman R.W."xsd:string
http://purl.uniprot.org/citations/16453294http://purl.uniprot.org/core/author"Greidinger E.L."xsd:string
http://purl.uniprot.org/citations/16453294http://purl.uniprot.org/core/author"Bejarano P."xsd:string
http://purl.uniprot.org/citations/16453294http://purl.uniprot.org/core/author"Hogenmiller S."xsd:string
http://purl.uniprot.org/citations/16453294http://purl.uniprot.org/core/author"Jaimes K."xsd:string
http://purl.uniprot.org/citations/16453294http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/16453294http://purl.uniprot.org/core/name"Arthritis Rheum"xsd:string
http://purl.uniprot.org/citations/16453294http://purl.uniprot.org/core/pages"661-669"xsd:string
http://purl.uniprot.org/citations/16453294http://purl.uniprot.org/core/title"A murine model of mixed connective tissue disease induced with U1 small nuclear RNP autoantigen."xsd:string
http://purl.uniprot.org/citations/16453294http://purl.uniprot.org/core/volume"54"xsd:string
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