Circadian clock disruption in autoimmune thyroiditis.

IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM European Thyroid Journal Pub Date : 2023-08-25 Print Date: 2023-10-01 DOI:10.1530/ETJ-23-0035
Jinrong Fu, Zihao Fan, Liang He, Qian Liu, He Liu, Yushu Li, Haixia Guan
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Abstract

Objective: A vicious cycle between circadian disruption and escalating immune responses has been described in diverse inflammatory disease. The current study aimed to explore the role of circadian clock disruption in autoimmune thyroiditis (AIT).

Methods: Thirty AIT patients and 30 controls were enrolled and biopsied for thyroid tissues. Alterations of core clock genes expression in AIT thyroid tissues, and its association with serum and tissue inflammatory biomarkers were assessed. For animal studies, C57BL/6J mice administered with porcine thyroglobulin or PBS (as control) combined with adjuvants were sacrificed at four time points to investigate the circadian characteristic of experimental autoimmune thyroiditis (EAT). Light shift (LS) conditions were used to explore the influence of external circadian disturbance on EAT.

Results: The expression of clock genes BMAL1 and PER2 was significantly reduced in thyroid tissues from AIT patients and was negatively correlated to levels of thyroid peroxidase antibodies. In mouse models, diurnal fluctuations of proinflammatory cytokines were demonstrated, and further exposing mice to LS led to overproduction of TNF-α, IFN-γ, and anti-thyroglobulin antibodies. Circadian analysis revealed significant oscillations of Bmal1, Clock, Per2, Cry1, Ror, and Rev-erb, which was broadly disturbed in EAT, LS, and EAT + LS groups.

Conclusions: This study demonstrates that expression pattern of clock genes was disrupted in AIT thyroid, and chronic circadian disruption may aggravate the inflammatory responses in AIT. Whether maintaining a regular circadian rhythm can alleviate autoimmune thyroid diseases warrants further research.

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自身免疫性甲状腺炎的昼夜节律紊乱。
目的:在各种炎症性疾病中,昼夜节律紊乱和免疫反应升级之间存在恶性循环。本研究旨在探讨昼夜节律时钟破坏在自身免疫性甲状腺炎(AIT)中的作用。评估了AIT甲状腺组织中核心时钟基因表达的变化及其与血清和组织炎症生物标志物的关系。在动物研究中,在四个时间点处死施用猪甲状腺球蛋白或PBS(作为对照)与佐剂联合的C57BL/6J小鼠,以研究实验性自身免疫性甲状腺炎(EAT)的昼夜节律特征。结果:AIT患者甲状腺组织中时钟基因BMAL1和PER2的表达显著降低,且与甲状腺过氧化物酶抗体水平呈负相关。在小鼠模型中,证明了促炎细胞因子的昼夜波动,进一步将小鼠暴露于LS会导致TNF-α、IFN-γ和抗甲状腺球蛋白抗体的过量产生。昼夜节律分析揭示了Bmal1、Clock、Per2、Cry1、Ror和Rev-erb的显著振荡,这些振荡在EAT、LS和EAT+LS组中受到广泛干扰。结论:本研究表明,AIT甲状腺中时钟基因的表达模式被破坏,慢性昼夜节律紊乱可能加剧AIT的炎症反应。保持规律的昼夜节律是否可以缓解自身免疫性甲状腺疾病,值得进一步研究。
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来源期刊
European Thyroid Journal
European Thyroid Journal Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
6.70
自引率
2.10%
发文量
156
期刊介绍: The ''European Thyroid Journal'' publishes papers reporting original research in basic, translational and clinical thyroidology. Original contributions cover all aspects of the field, from molecular and cellular biology to immunology and biochemistry, from physiology to pathology, and from pediatric to adult thyroid diseases with a special focus on thyroid cancer. Readers also benefit from reviews by noted experts, which highlight especially active areas of current research. The journal will further publish formal guidelines in the field, produced and endorsed by the European Thyroid Association.
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