{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:55:23Z","timestamp":1773662123314,"version":"3.50.1"},"reference-count":33,"publisher":"The Endocrine Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,3,1]]},"abstract":"<jats:p>One approach to prevent tissue destruction by autoimmune attack in organ-specific autoimmune diseases is to protect the target tissue from autoimmune reaction, regardless of its persistent activity. To provide proof-of-principle for the feasibility of this approach, the immunoregulatory molecules, TNF-related apoptosis-inducing ligand (TRAIL) and indoleamine 2, 3-dioxygenase, were expressed in the thyroid glands using adenovirus vector in nonobese diabetic-H2h4 mice that spontaneously develop thyroiditis. Mice were anesthetized, and the thyroid glands were exposed by neck dissection, followed by in situ infection with adenovirus vector (5 \u00d7 1010 particles per mouse) twice or thrice, starting 1 d or 4 wk before mice were supplied with sodium iodine (NaI) water. After 8 wk NaI provision, the extent of thyroiditis, serum titers of antithyroglobulin antibodies, and cytokine expression in the spleen were examined. In situ infection of adenovirus expressing TRAIL or indoleamine 2, 3-dioxygenase, but not green fluorescent protein, significantly suppressed thyroiditis scores. However, antithyroglobulin antibody titers and expression levels of cytokines (interferon-\u03b3 and IL-4) in the spleen remained unaltered. Importantly, adenovirus infection 4 wk after NaI provision was also effective at suppressing thyroiditis. The suppressive effect of TRAIL appears to be mediated at least partly by accumulation of CD4+Foxp3+ regulatory T cells into the thyroid glands. Thus, localized expression of immunoregulatory molecules efficiently protected the thyroid glands from autoimmune attack without changing the systemic autoimmunity in nonobese diabetic-H2h4 mice. This kind of immunological intervention, although it does not suppress autoimmune reactivity, may have a potential for treating organ-specific autoimmune diseases.<\/jats:p><jats:p>The feasibility of in situ expression of the immuno-regulatory molecules to prevent tissue destruction by autoimmune attack in organ-specific autoimmune diseases is discussed.<\/jats:p>","DOI":"10.1210\/en.2008-0702","type":"journal-article","created":{"date-parts":[[2008,11,7]],"date-time":"2008-11-07T01:55:58Z","timestamp":1226022958000},"page":"1545-1551","source":"Crossref","is-referenced-by-count":16,"title":["Expression of Immunoregulatory Molecules by Thyrocytes Protects Nonobese Diabetic-H2h4 Mice from Developing Autoimmune Thyroiditis"],"prefix":"10.1210","volume":"150","author":[{"given":"Mami","family":"Nakahara","sequence":"first","affiliation":[{"name":"Department of Medical Gene Technology (M.N., Y.N., O.S., R.S.), Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, 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