Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, PR China.
Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, PR China.
Clin Immunol. 2018 May;190:41-52. doi: 10.1016/j.clim.2018.02.006. Epub 2018 Feb 23.
Estrogens play important roles in autoimmune thyroiditis, but it remains unknown which estrogen receptor (ER) subtype mediates the stimulatory effects. Herein we treated ovariectomized mice with ERα or ERβ selective agonist followed by thyroglobulin-immunization to induce experimental autoimmune thyroiditis (EAT), and observed the aggravation of EAT after diarylpropionitrile (DPN, ERβ selective agonist) administration. The mRNA levels of interleukin(IL)-17A, IL-21 and RORγt and percentages of T helper (Th) 17 cells were up-regulated in the splenocytes of DPN-treated mice. Activated ERβ was found directly binding to IL-17A and IL-21 gene promoters, and also indirectly promoting IL-21 and RORγt gene transcription through interaction with NF-κB. The expressions of co-stimulatory molecules were increased on antigen-presenting cells (APCs) after DPN administration. It suggests that ERβ is the predominant ER subtype responsible for EAT development, and its activation may enhance Th17-type responses through genomic pathways and alteration of APCs' activities.
雌激素在自身免疫性甲状腺炎中发挥重要作用，但哪种雌激素受体（ER）亚型介导其刺激作用尚不清楚。本研究用 ERα 或 ERβ 选择性激动剂处理去卵巢小鼠，然后用甲状腺球蛋白免疫诱导实验性自身免疫性甲状腺炎（EAT），观察到二芳基丙腈（DPN，ERβ 选择性激动剂）给药后 EAT 加重。DPN 处理小鼠的脾细胞中白细胞介素（IL）-17A、IL-21 和 RORγt 的 mRNA 水平上调，Th17 细胞的百分比增加。激活的 ERβ 被发现直接结合到 IL-17A 和 IL-21 基因启动子上，并通过与 NF-κB 相互作用间接促进 IL-21 和 RORγt 基因转录。DPN 给药后抗原呈递细胞（APC）上共刺激分子的表达增加。这表明 ERβ 是导致 EAT 发展的主要 ER 亚型，其激活可能通过基因组途径和 APC 活性的改变增强 Th17 型反应。
