{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T21:21:20Z","timestamp":1780521680938,"version":"3.54.1"},"reference-count":27,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,11,1]]},"abstract":"<jats:p>Iodine-induced experimental autoimmune thyroiditis in the nonobese diabetic (NOD)-H2h4 mouse is a prototype of animal models of Hashimoto's thyroiditis in humans. Recent studies have shown the resistance to thyroiditis of NOD-H2h4 mice genetically deficient for either IL-17 or interferon (IFN)-\u03b3, implicating both of T helper type 1 (Th1) and Th17 immune responses in disease pathogenesis. However, we hypothesized that robust induction of a single arm of effector T cells (either Th1 or Th17) might be sufficient for inducing thyroiditis in NOD-H2h4 mice. To address this hypothesis, enhanced immune responses consisting of either Th1 or Th17 were induced by anti-CD25 antibody-mediated depletion of regulatory T cells (Treg) in thyroiditis-resistant IL-17 knockout (KO) or IFN-\u03b3 receptor (IFN-\u03b3R) KO, respectively, NOD-H2h4 mice. Depletion of Treg in IL-17 KO mice (i.e. Th1 enhancement) elicited antithyroglobulin autoantibodies and thyroiditis. Immunohistochemical analysis of the thyroid glands revealed the similar intrathyroidal lymphocyte infiltration patterns, with CD4+ T and CD19+ B cells being dominant between the wild-type and Treg-depleted IL-17 KO mice. In contrast, Treg-depleted IFN-\u03b3R KO mice remained thyroiditis resistant. Intracellular cytokine staining assays showed differentiation of Th1 cells in IL-17 KO mice but not of Th17 cells in IFN-\u03b3R KO mice. Our findings demonstrate that a robust Th1 immune response can by itself induce thyroiditis in otherwise thyroiditis-resistant IL-17 KO mice. Thus, unlike Th17 cells in IFN-\u03b3R KO mice, Th1 cells enhanced by Treg depletion can be sustained and induce thyroiditis.<\/jats:p>","DOI":"10.1210\/en.2011-1356","type":"journal-article","created":{"date-parts":[[2011,8,24]],"date-time":"2011-08-24T02:26:51Z","timestamp":1314152811000},"page":"4448-4454","source":"Crossref","is-referenced-by-count":33,"title":["Induction of Autoimmune Thyroiditis by Depletion of CD4+CD25+ Regulatory T Cells in Thyroiditis-Resistant IL-17, But Not Interferon-\u03b3 Receptor, Knockout Nonobese Diabetic-H2h4 Mice"],"prefix":"10.1210","volume":"152","author":[{"given":"Ichiro","family":"Horie","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine (I.H., H.S., Y.N.), and Department of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan"},{"name":"Division of Immunology, Endocrinology, and Metabolism (I.H., N.A.), and Department of Medical and Dental Sciences, Nagasaki 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Nagayama","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine (I.H., H.S., Y.N.), and Department of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2011,8,23]]},"reference":[{"key":"2020071613024852500_B1","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1084\/jem.178.3.793","article-title":"I-E+ nonobese diabetic mice develop insulitis and diabetes.","volume":"178","author":"Podolin","year":"1993","journal-title":"J Exp Med"},{"key":"2020071613024852500_B2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1006\/jaut.1999.0272","article-title":"Spontaneous autoimmune thyroiditis in NOD.H-2h4 mice.","volume":"12","author":"Braley-Mullen","year":"1999","journal-title":"J 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