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

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

机构信息

Department of Ophthalmic Center, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, 330006, Jiangxi, China.

出版信息

Mol Med. 2024 Nov 26;30(1):233. doi: 10.1186/s10020-024-01004-5.

DOI:10.1186/s10020-024-01004-5

PMID:39592944

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11590473/

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.

摘要

背景

过敏性结膜炎（AC）影响人们的日常生活和工作，尤其对儿童的健康影响较大。虽然相关研究较少，但 Th17/Treg 失衡在 AC 发病中起重要作用。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。采用流式细胞术检测 Th17 和 Treg 细胞比例。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 信号水平。

结果

在 AC 状态下，观察到 Th17/Treg 细胞平衡失调、TWEAK/Fn14 信号水平升高和结膜炎症。TWEAK 敲低后，AC 小鼠 Th17 细胞分化受到抑制，Treg 细胞分化受到促进，AC 症状得到缓解。此外，TWEAK 敲低导致 AC 模型中 Nrf2/HO-1 信号通路增强。Nrf2 抑制剂处理逆转了 TWEAK 敲低引起的这些变化。因此，TWEAK/Fn14 通过调节 Nrf2/HO-1 通路影响 AC 小鼠模型中的 Th17/Treg 细胞平衡和结膜炎。