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During inflammation, cytokines upregulate\n                      <jats:italic toggle=\"yes\">DUOX<\/jats:italic>\n                      gene expression in the airway and the intestine, suggesting a role for these proteins in innate immunity. It was previously demonstrated that interleukin-4 (IL-4) upregulates\n                      <jats:italic toggle=\"yes\">DUOX<\/jats:italic>\n                      gene expression in thyrocytes. Although the role of IL-4 in autoimmune thyroid diseases has been studied extensively, the effects of IL-4 on thyroid physiology remain largely unknown. Therefore, a new animal model was generated to study the impact of IL-4 on thyroid function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Transgenic (Thyr-IL-4) mice with thyroid-targeted expression of murine IL-4 were generated. Transgene expression was verified at the mRNA and protein level in thyroid tissues and primary cultures. The phenotype of the Thyr-IL-4 animals was characterized by measuring serum thyroxine (T4) and thyrotropin levels and performing thyroid morphometric analysis, immunohistochemistry, whole transcriptome sequencing, quantitative reverse transcription polymerase chain reaction, and\n                      <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                      thyroid function assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Thyrocytes from two Thyr-IL-4 mouse lines (#30 and #52) expressed IL-4, which was secreted into the extracellular space. Although 10-month-old transgenic animals had T4 and thyrotropin serum levels in the normal range, they had altered thyroid follicular structure with enlarged follicles composed of elongated thyrocytes containing numerous endocytic vesicles. These follicles were positive for T4 staining the colloid, indicating their capacity to produce thyroid hormones. RNA profiling of Thyr-IL-4 thyroid samples revealed modulation of multiple genes involved in inflammation, while no major leukocyte infiltration could be detected. Upregulated expression of\n                      <jats:italic toggle=\"yes\">Duox1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Duoxa1<\/jats:italic>\n                      , and the pendrin anion exchanger gene (\n                      <jats:italic toggle=\"yes\">Slc26a4<\/jats:italic>\n                      ) was detected. In contrast, the iodide symporter gene\n                      <jats:italic toggle=\"yes\">Slc5a5<\/jats:italic>\n                      was markedly downregulated resulting in impaired iodide uptake and reduced thyroid hormone levels in transgenic thyroid tissue. Hydrogen peroxide production was increased in Thyr-IL-4 thyroid tissue compared with wild-type animals, but no significant oxidative stress could be detected.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      This is the first study to show that ectopic expression of IL-4 in thyroid tissue upregulates\n                      <jats:italic toggle=\"yes\">Duox1<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">Duoxa1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Slc26a4<\/jats:italic>\n                      expression in the thyroid. The present data demonstrate that IL-4 could affect thyroid morphology and function, mainly by downregulating\n                      <jats:italic toggle=\"yes\">Slc5a5<\/jats:italic>\n                      expression, while maintaining a normal euthyroid phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2016.0106","type":"journal-article","created":{"date-parts":[[2016,9,7]],"date-time":"2016-09-07T00:58:25Z","timestamp":1473209905000},"page":"1499-1512","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Overexpression of Interleukin-4 in the Thyroid of Transgenic Mice Upregulates the Expression of\n                    <i>Duox1<\/i>\n                    and the Anion Transporter Pendrin"],"prefix":"10.1177","volume":"26","author":[{"given":"Zineb","family":"Eskalli","sequence":"first","affiliation":[{"name":"Universit\u00e9 libre de Bruxelles 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