TWEAK/Fn14 disrupts Th17/Treg balance and aggravates conjunctivitis by inhibiting the Nrf2/HO-1 pathway in allergic conjunctivitis mice.

IF 6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Medicine Pub Date : 2024-11-26 DOI:10.1186/s10020-024-01004-5

Yang Yang, Yuezhi Zhang, Jingfan Fu, Xiaolong Yin

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Abstract

Background: Allergic conjunctivitis (AC) affects people's daily life and work, especially the health of children. Although there are few relevant studies, Th17/Treg imbalance plays an important role in AC development. The aim of this study was to elucidate the effect of TWEAK/Fn14 on AC and Th17/Treg balance.

Methods: Ovalbumin induced AC mouse model was utilized to observe the mechanism of TWEAK/Fn14 in vivo. Conjunctivitis was evaluated by hematoxylin-eosin staining, toluidine blue staining and AC clinical score. Flow cytometry was used to measure Th17 and Treg cell ratios. The level of Th17/Treg balance related factors and Nrf2/HO-1 signal was detected by ELISA, WB, qRT-PCR and immunohistochemistry.

Results: In the AC state, disruption of Th17/Treg cell balance, increased TWEAK/Fn14 signaling level and conjunctival inflammation were observed. After TWEAK knockdown, Th17 cell differentiation was inhibited, Treg cell differentiation was promoted, and AC symptoms were alleviated in AC mice. Moreover, TWEAK knockdown caused an enhancement of the Nrf2/HO-1 signaling pathway in the AC models. Treatment with Nrf2 inhibitor reversed these changes induced by TWEAK knockdown. Therefore, TWEAK/Fn14 regulated the Nrf2/HO-1 pathway to affect Th17/Treg cell balance and conjunctivitis in AC mouse models.

Conclusion: In summary, TWEAK/Fn14 caused Th17/Treg imbalance by inhibiting Nrf2/HO-1 pathway, which might be one potential mechanism of the exacerbation of AC.

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TWEAK/Fn14 通过抑制过敏性结膜炎小鼠的 Nrf2/HO-1 通路，破坏 Th17/Treg 平衡并加重结膜炎。

背景：过敏性结膜炎（AC）影响着人们的日常生活和工作，尤其是儿童的健康：过敏性结膜炎（AC）影响着人们的日常生活和工作，尤其是儿童的健康。尽管相关研究较少，但Th17/Treg失衡在过敏性结膜炎的发病中起着重要作用。本研究旨在阐明TWEAK/Fn14对AC和Th17/Treg平衡的影响：方法：利用卵清蛋白诱导的 AC 小鼠模型观察 TWEAK/Fn14 在体内的作用机制。通过苏木精-伊红染色、甲苯胺蓝染色和AC临床评分评估结膜炎。流式细胞术用于测量 Th17 细胞和 Treg 细胞的比例。通过ELISA、WB、qRT-PCR和免疫组化检测Th17/Treg平衡相关因子和Nrf2/HO-1信号的水平：结果：在AC状态下，观察到Th17/Treg细胞平衡被破坏、TWEAK/Fn14信号水平升高和结膜炎症。敲除 TWEAK 后，Th17 细胞分化受到抑制，Treg 细胞分化得到促进，AC 小鼠的 AC 症状得到缓解。此外，TWEAK敲除还增强了AC模型中的Nrf2/HO-1信号通路。用 Nrf2 抑制剂治疗可逆转 TWEAK 敲除引起的这些变化。因此，TWEAK/Fn14调节了Nrf2/HO-1通路，从而影响了AC小鼠模型中Th17/Treg细胞的平衡和结膜炎：总之，TWEAK/Fn14通过抑制Nrf2/HO-1通路导致Th17/Treg细胞失衡，这可能是AC恶化的潜在机制之一。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Medicine 医学-生化与分子生物学

CiteScore

8.60

自引率

0.00%

发文量

137

审稿时长

1 months

期刊介绍： Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.