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起重要作用，但尚不清楚哪种雌激素受体 (ER) 亚型介导刺激作用。在此，我们用 ERα 或 ERβ 选择性激动剂治疗切除卵巢的小鼠，然后进行甲状腺球蛋白免疫以诱导实验性自身免疫性甲状腺炎 (EAT)，并观察在二芳基丙腈（DPN，ERβ 选择性激动剂）给药后 EAT 的加重。在 DPN 处理的小鼠脾细胞中，白细胞介素 (IL)-17A、IL-21 和 RORγt 的 mRNA 水平以及 T 辅助 (Th) 17 细胞的百分比上调。发现活化的 ERβ 直接与 IL-17A 和 IL-21 基因启动子结合，并且还通过与 NF-κB 的相互作用间接促进 IL-21 和 RORγt 基因转录。DPN 给药后，共刺激分子在抗原呈递细胞 (APC) 上的表达增加。这表明 ERβ 是负责 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。