Vitamin D ameliorates NETosis and Th17/Treg imbalance in experimental autoimmune thyroiditis

IF 3.2 4区医学 Q3 IMMUNOLOGY

Immunology letters Pub Date : 2026-08-01 Epub Date: 2026-02-28 DOI:10.1016/j.imlet.2026.107156

Hai-Yan Yang , Xi-Zhen Wu , Yu-Ping Liu , Gui-Yang Jiang , Ying-Fen Qin , Xing-Huan Liang , Zuo-Jie Luo

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引用次数: 0

Abstract

Background

Neutrophil extracellular traps (NETs) have been implicated in various autoimmune diseases; however, their role in Hashimoto's thyroiditis (HT) remains poorly understood. This study aimed to characterize NETs formation, explore its association with thyroid dysfunction and adaptive immunity, and evaluate the therapeutic potential of vitamin D (VD) in experimental autoimmune thyroiditis (EAT).

Methods

EAT was induced in BALB/c mice via thyroglobulin immunization combined with excess iodine intake. The VD group received additional intraperitoneal calcitriol supplementation. Thyroid histopathology, MHC-II expression, thyroid antibodies (TGAb and TPOAb), plasma DNase-I and 1,25(OH)₂D₃ levels, NETs formation, and splenic T cell subsets (Th17, Treg, Th1, Th2) and cytokines were assessed. Parallel experiments were conducted using neutrophils isolated from HT patients.

Results

Neutrophils from both EAT mice and HT patients exhibited enhanced NETosis compared to controls. EAT mice showed lower levels of DNase-I, 1,25(OH)₂D₃, Treg, and Th1 cells, along with higher Th17 and Th2 cells, elevated Th17/Treg ratio, and heightened thyroid MHC-II expression. NETs levels positively correlated with Th17, Th2, and MHC-II expression, and negatively with Treg, Th1, 1,25(OH)₂D₃, and DNase-I. VD supplementation mitigated thyroiditis and TPOAb levels, suppressed NETs formation, and reduced the Th17/Treg ratio and IL-17 levels.

Conclusions

NETs contribute to Th17 bias and MHC-II over-expression in HT, suggesting a role in shaping the adaptive immune response. Vitamin D restrains NETosis and restores T-cell homeostasis, highlighting its potential as an adjunctive therapy for HT.

查看原文本刊更多论文

维生素D改善实验性自身免疫性甲状腺炎的NETosis和Th17/Treg失衡。

背景：中性粒细胞胞外陷阱（NETs）与多种自身免疫性疾病有关；然而，它们在桥本甲状腺炎（HT）中的作用仍然知之甚少。本研究旨在表征NETs的形成，探讨其与甲状腺功能障碍和适应性免疫的关系，并评估维生素D （VD）在实验性自身免疫性甲状腺炎（EAT）中的治疗潜力。方法：通过甲状腺球蛋白免疫联合过量碘摄入诱导BALB/c小鼠发生EAT。VD组在腹腔内补充骨化三醇。评估甲状腺组织病理学、MHC-II表达、甲状腺抗体（TGAb和TPOAb）、血浆dna - i和1,25（OH）₂D₃水平、NETs形成、脾脏T细胞亚群（Th17、Treg、Th1、Th2）和细胞因子。利用从HT患者中分离的中性粒细胞进行平行实验。结果：与对照组相比，进食小鼠和HT患者的中性粒细胞均表现出增强的NETosis。结果表明，进食小鼠的dna - i、1,25（OH）₂D₃、Treg、Th1细胞水平降低，Th17、Th2细胞水平升高，Th17/Treg比例升高，甲状腺MHC-II表达升高。NETs水平与Th17、Th2和MHC-II的表达呈正相关，与Treg、Th1、1,25（OH）₂D₃和DNase-I呈负相关。补充VD可减轻甲状腺炎和TPOAb水平，抑制NETs形成，降低Th17/Treg比率和IL-17水平。结论：NETs导致Th17偏倚和MHC-II在HT中的过度表达，提示其在形成适应性免疫反应中起作用。维生素D抑制NETosis和恢复t细胞稳态，突出其作为HT辅助治疗的潜力。

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来源期刊

Immunology letters 医学-免疫学

CiteScore

7.60

自引率

0.00%

发文量

审稿时长

44 days

期刊介绍： Immunology Letters provides a vehicle for the speedy publication of experimental papers, (mini)Reviews and Letters to the Editor addressing all aspects of molecular and cellular immunology. The essential criteria for publication will be clarity, experimental soundness and novelty. Results contradictory to current accepted thinking or ideas divergent from actual dogmas will be considered for publication provided that they are based on solid experimental findings. Preference will be given to papers of immediate importance to other investigators, either by their experimental data, new ideas or new methodology. Scientific correspondence to the Editor-in-Chief related to the published papers may also be accepted provided that they are short and scientifically relevant to the papers mentioned, in order to provide a continuing forum for discussion.