Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan; Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei 11031, Taiwan.
Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11031, Taiwan.
Life Sci. 2022 Jan 1;288:120172. doi: 10.1016/j.lfs.2021.120172. Epub 2021 Nov 23.
Patients with chronic hepatitis C are frequently treated with interferon (IFN)-α. Autoimmune thyroid disease occurs in 20% ~ 40% of IFN-α-treated patients. In this study, the effects of IFN-α administration on triggering and regulating autoimmune thyroiditis in various animal models were evaluated.
Exogenous IFN-α was given to naive CBA mice, and both thyroglobulin (TG) immunization-induced (CBA) and spontaneous autoimmune thyroiditis (NOD·H-2 h4) models. Thyroid function, and anti-thyroglobulin antibody (ATA) and B-cell-activating factor (BAFF) levels were measured. Alterations in transcriptome profiles were analyzed.
In the TG-induced thyroiditis model, IFN-α administration reduced plasma free thyroxine levels but did not alter ATA titers, BAFF levels, or the severity of histological changes. Interestingly, even without changes in thyroid functions, four of eight mice in the IFN-α alone group exhibited thyroiditis compared to the control group. Immunologically, mice in the IFN-α group exhibited profound CD3 cell infiltration in the thyroid and higher plasma BAFF levels compared to the control group. Meanwhile, pathological and serological alterations after IFN-α administration were not observed in the NOD·H-2 h4 model. An RNA sequencing analysis revealed that immunoregulatory signatures were not excited by IFN-α treatment in naive CBA mice. Meanwhile, innate and adaptive immunity, inflammatory cytokine, chemokine, and cell-killing signaling pathways were all stimulated by IFN-α administration after TG immunization of CBA mice.
We confirmed the remarkable effects of IFN-α in both initiating thyroid immunity and modulating thyroid function and immunoregulatory signatures in established autoimmune thyroiditis. We suggest that IFN-α should be administered with caution in clinical settings.
慢性丙型肝炎患者常接受干扰素（IFN）-α治疗。自身免疫性甲状腺疾病发生在 20%~40%的 IFN-α治疗患者中。在这项研究中，评估了 IFN-α给药对各种动物模型中触发和调节自身免疫性甲状腺炎的影响。
将外源性 IFN-α给予未致敏的 CBA 小鼠，以及甲状腺球蛋白（TG）免疫诱导（CBA）和自发性自身免疫性甲状腺炎（NOD·H-2 h4）模型。测量甲状腺功能以及抗甲状腺球蛋白抗体（ATA）和 B 细胞激活因子（BAFF）水平。分析转录组谱的变化。
在 TG 诱导的甲状腺炎模型中，IFN-α给药降低了血浆游离甲状腺素水平，但未改变 ATA 效价、BAFF 水平或组织学变化的严重程度。有趣的是，即使甲状腺功能没有变化，IFN-α 单独组的 8 只小鼠中有 4 只表现出甲状腺炎，而对照组没有。免疫上，IFN-α 组的小鼠甲状腺中 CD3 细胞浸润明显增加，血浆 BAFF 水平高于对照组。同时，IFN-α 给药后在 NOD·H-2 h4 模型中未观察到病理和血清学改变。RNA 测序分析显示，IFN-α 处理在未致敏的 CBA 小鼠中未激发免疫调节特征。同时，IFN-α 给药后在 CBA 小鼠 TG 免疫后，固有和适应性免疫、炎症细胞因子、趋化因子和细胞杀伤信号通路均被激活。
我们证实了 IFN-α在启动甲状腺免疫和调节已建立的自身免疫性甲状腺炎中的甲状腺功能和免疫调节特征方面的显著作用。我们建议在临床环境中谨慎使用 IFN-α。
