{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:57:18Z","timestamp":1791295038014,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2008,5,2]],"date-time":"2008-05-02T00:00:00Z","timestamp":1209686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2008,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The present study aimed to determine the effect of canine CTLA4Ig on canine autoimmune thyroiditis. In a previous study, we established a canine model of autoimmune thyroiditis by immunizing normal dogs with bovine thyroglobulin. An <jats:italic>in vitro<\/jats:italic> study using recombinant CTLA4Ig revealed that this protein can inhibit the expression of Th1\u2010type cytokines and the pro\u2010inflammatory cytokines tested.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>As a result of the <jats:italic>in vitro<\/jats:italic> study, we constructed therapeutic CTLA4Ig\/silica\u2010nanoparticles and applied them to the treatment of experimentally induced canine autoimmune thyroiditis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Gene therapy resulted in significant reductions in anti\u2010canine\u2010thyroglobulin autoantibody titer, anti\u2010T4 antibody titer and T\u2010cell proliferation against thyroglobulin and in the mRNA expressions of interleukin\u201018 in fresh peripheral blood mononuclear cells (PBMC) from all dogs. There was also a significant reduction compared to day 0 in tumor necrosis factor\u2010\u03b1 and interferon\u2010\u03b3 levels in the supernatant from cultured PBMC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The CTLA4Ig\u2010induced suppression of Th1 cytokines is relatively more significant than it appears because autoimmune thyroiditis is a Th1\u2010polarized disease. Thus, CTLA4Ig can improve Th1\/Th2 cytokine balance in autoimmune thyroiditis by downregulating Th1 cytokines. 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