|Abstract : The role of IL-4 has long been studied in the context of autoimmune thyroid disease (ATID). Two extreme manifestations of AITD are Hashimoto's thyroiditis and Graves' disease, both characterized by lymphocytic infiltration and autoantibodies directed against thyroid markers.
In order to study the role of IL-4 on thyroid function, we generated a new transgenic mouse, Thyr-IL-4, overexpressing IL-4 in the thyroid tissue. Overexpression of Duox1 was related to increase hydrogen peroxide production in transgenic thyroid tissues without causing cellular damage. Decrease in Nis expression was associated with hypothyroid phenotype under low iodine diet. After immunization against the TSH receptor, we observed increased leukocyte infiltration in Thyr-IL-4 mice.
To promote ROS-mediated cellular damage, mice will be treated with thiocyanate under a selenium-deficient diet. To potentiate IL-4 signaling cascade activation, Thyr-IL-4 mice will be crossed with IL-13Ra2-deficient mice. The combination of IL-4-mediated anti-apoptotic action and Duox1-dependent accumulation of ROS will be tested on thyroid tumor development by crossing Thyr-IL-4 mice with P53KO mice or different mouse models of thyroid cancers. Treatment with selenium-deficient diet or crossing with anti-oxidant deficient mice will be also tested. To better evaluate the role of IL-4 on AITD, transgenic mice will be breed with NOD.H2H4 mice or the new NOD.H2H4/hTSHrA developing spontaneous AITD.|
|Promoteur/Supervisor : Prof. DE DEKEN Xavier|
|Email : firstname.lastname@example.org|
|Site Web/Web site : http://duoxlab.iribhm.org/|
|Centre de recherche/Research center : IRIBHM - DUOX Lab|
|Faculté/Faculty : Faculty of Medicine/Faculté de Médecine|
|Ecole doctorale/Graduate Colleges : Biomedical and Pharmaceutical Science/Sciences biomédicales et pharmaceutiques|
|Ecole doctorale thématique/Graduate School (French Only): Biologie Cellulaire et Moléculaire, Biochimie (BCMB)|