{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:36:59Z","timestamp":1791898619503,"version":"4.3.4"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T00:00:00Z","timestamp":1138752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To test whether immunizing mice with autoantigens closely linked to mixed connective tissue disease (MCTD) could induce an MCTD\u2010like clinical syndrome distinguishable from systemic lupus erythematosus (SLE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Transgenic and knockout C57BL\/6\u2010derived mice were immunized subcutaneously at age 8\u201312 weeks with U1\u201370\u2010kd 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Immunization of C57BL\/6\u2010derived mice transgenic for human HLA\u2013DR4 with 70K and either CFA or U1 RNA led to anti\u201070K antibodies in 62% of mice (21 of 34), and diversified anti\u2010RNP immune responses. MCTD\u2010like lung disease also developed in 50% of immunized mice (17 of 34), and anti\u201070K antibodies were strongly correlated with lung disease. CFA and U1 RNA were comparably able to induce this syndrome. Mice deficient in Toll\u2010like receptor 3 (TLR\u20103) also developed this same syndrome when immunized with 70K and CFA. However, TLR\u20103<jats:sup>\u2212\/\u2212<\/jats:sup> mice failed to develop MCTD\u2010like lung disease when treated with 70K and U1 RNA. Rather, TLR\u20103<jats:sup>\u2212\/\u2212<\/jats:sup> mice immunized with 70K and U1 RNA developed an autoimmune syndrome characterized by glomerulonephritis typical of SLE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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\u201070K immunity and MCTD\u2010like lung disease. Of note, changes in innate immune signaling can cause the same trigger to lead to the development of SLE\u2010like nephritis rather than MCTD\u2010like lung disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.21566","type":"journal-article","created":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T21:17:57Z","timestamp":1138828677000},"page":"661-669","source":"Crossref","is-referenced-by-count":66,"title":["A murine model of mixed connective tissue disease induced with U1 small nuclear RNP autoantigen"],"prefix":"10.1002","volume":"54","author":[{"given":"Eric 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