Regulation of Tert methylation alleviates food allergy via regulating the Tert-IL10 signal pathway.

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-10-01 Epub Date: 2024-07-22 DOI:10.1007/s12026-024-09504-6

Haotao Zeng, Lingzhi Xu, Jiangqi Liu, Lihua Mo, Minyao Li, Shuo Song, Xuejie Xu, Shihan Miao, Miao Zhao, Pingchang Yang

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Abstract

Background: The cause of food allergy (FA) is still a mystery. Telomerases are involved in the regulation of immune responses. This study aims to gain an understanding of the contribution of telomerase reverse transcriptase (TERT) to the pathogenesis of FA.

Methods: A murine FA model was established with ovalbumin as the specific antigen. The role of TERT in regulating dendritic cell (DC) immune tolerogenic functions was evaluated in this murine model.

Results: We observed that the Tert promoter was at demethylation status and the Tert expression was elevated in DCs of FA mice. The Tert expression in DCs had a positive correlation with the FA response. TERT prevented the induction of Il10 expression in DCs. The immune tolerogenic functions of DCs were diminished by TERT. The immune tolerogenic functions of DC were restored by CpG by boosting the Tert promoter methylation. Administration of CpG promoted the therapeutic effects of allergen specific immunotherapy in FA mice.

Conclusions: Low levels of Il10 expression and high levels of Tert expression were observed in intestinal DCs of FA mice. CpG exposure restored the expression of Il10 and increased the therapeutic benefits of allergen-specific immunotherapy.

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通过调节 Tert-IL10 信号通路来调节 Tert 甲基化，从而缓解食物过敏。

背景：食物过敏症（FA）的病因至今仍是一个谜。端粒酶参与调节免疫反应。本研究旨在了解端粒酶逆转录酶（TERT）对食物过敏症发病机制的贡献：方法：以卵清蛋白为特异性抗原建立了小鼠FA模型。方法：以卵清蛋白为特异性抗原建立了小鼠FA模型，评估了TERT在调节树突状细胞（DC）免疫耐受功能中的作用：结果：我们观察到，在 FA 小鼠的 DC 中，Tert 启动子处于去甲基化状态，Tert 表达升高。Tert在DCs中的表达与FA反应呈正相关。TERT阻止了Il10在DCs中的诱导表达。TERT削弱了DCs的免疫耐受功能。CpG通过促进Tert启动子甲基化恢复了DC的免疫耐受功能。CpG能促进过敏原特异性免疫疗法对FA小鼠的治疗效果：结论：在 FA 小鼠的肠道 DC 中观察到低水平的 Il10 表达和高水平的 Tert 表达。结论：在 FA 小鼠的肠道直流细胞中观察到了低水平的 Il10 表达和高水平的 Tert 表达，CpG 暴露可恢复 Il10 的表达并提高过敏原特异性免疫疗法的治疗效果。

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