芳香烃受体
免疫系统
甲状腺炎
内分泌学
肿瘤坏死因子α
甲状腺
内科学
自身免疫性甲状腺炎
CYP1B1型
甲状腺球蛋白
白细胞介素
免疫学
生物
化学
转录因子
细胞因子
医学
细胞色素P450
新陈代谢
生物化学
基因
作者
Zhengzheng Liao,Xianzhong Zeng,Xiaoling Guo,Qing Shi,Zhonglin Tang,Ping Li,Cuiyun Chen,Mengxia Chen,Jianrong Chen,Jixiong Xu,Yaojun Cai
标识
DOI:10.1016/j.ejphar.2024.176588
摘要
Hashimoto's thyroiditis (HT) is the most frequent autoimmune disorder. Growing work points to the involvement of aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, in the regulation of immune homeostasis. However, the roles of AhR and its ligands in HT remains unclear. In this study, we leveraged public human database analyses to postulate that the AhR expression was predominantly in thyroid follicular cells, correlating significantly with the thyroid infiltration levels of multiple immune cells in HT patients. Using a thyroglobulin-induced HT mouse model and in vitro thyroid follicular epithelial cell cultures, we found a significant downregulation of AhR expression in thyrocytes both in vivo and in vitro. Conversely, activating AhR by FICZ, a natural AhR ligand, mitigated inflammation and apoptosis in thyrocytes in vitro and conferred protection against HT in mice. RNA sequencing (RNA-seq) of thyroid tissues indicated that AhR activation moderated HT-associated immune or inflammatory signatures. Further, immunoinfiltration analysis indicated that AhR activation regulated immune cell infiltration in the thyroid of HT mice, such as suppressing cytotoxic CD8+ T cell infiltration and promoting anti-inflammatory M2 macrophage polarization. Concomitantly, the expression levels of interleukin-2 (IL-2), a lymphokine that downregulates immune responses, were typically decreased in HT but restored upon AhR activation. In silico validation substantiated the binding interaction between AhR and IL-2. In conclusion, targeting the AhR with FICZ regulates IL-2 and immune infiltration to alleviate experimental HT, shedding new light on the therapeutic intervention of this prevalent disease.
科研通智能强力驱动
Strongly Powered by AbleSci AI