Laboratory of Allergy, Allergy Research Group, Instituto de Investigación Biomédica de Málaga-Plataforma BIONAND (IBIMA-BIONAND), Málaga, Spain.
Department of Medicine, Universidad de Málaga (UMA), Málaga, Spain.
Front Immunol. 2023 Jun 2;14:1165852. doi: 10.3389/fimmu.2023.1165852. eCollection 2023.
Lipid transfer proteins (LTPs) are allergens found in a wide range of plant-foods. Specifically, Pru p 3, the major allergen of peach, is commonly responsible for severe allergic reactions. The need for new alternatives to conventional food allergy treatments, like restrictive diets, suggests allergen immunotherapy as a promising option. It has been demonstrated that sublingual immunotherapy (SLIT) with synthetic glycodendropeptides, such as D1ManPrup3, containing mannose and Pru p 3 peptides induced tolerance in mice and that the persistence of this effect depends on treatment dose (2nM or 5nM). Moreover, it produces changes associated with differential gene expression and methylation profile of dendritic cells, as well as phenotypical changes in regulatory T cells (Treg). However, there are no works addressing the study of epigenetic changes in terms of methylation in the cell subsets that sustain tolerant responses, Treg. Therefore, in this work, DNA methylation changes in splenic-Treg from Pru p 3 anaphylactic mice were evaluated.
It was performed by whole genome bisulphite sequencing comparing SLIT-D1ManPrup3 treated mice: tolerant (2nM D1ManPrup3), desensitized (5nM D1ManPrup3), and sensitized but not treated (antigen-only), with anaphylactic mice.
Most of the methylation changes were found in the gene promoters from both SLIT-treated groups, desensitized (1,580) and tolerant (1,576), followed by the antigen-only (1,151) group. Although tolerant and desensitized mice showed a similar number of methylation changes, only 445 genes were shared in both. Remarkably, interesting methylation changes were observed on the promoter regions of critical transcription factors for Treg function like , , , , and . In fact, was observed exclusively as hypomethylated in tolerant group, whereas was only hypomethylated in the desensitized mice.
In conclusion, diverse D1ManPrup3 doses induce different responses (tolerance or desensitization) in mice, which are reflected by differential methylation changes in Tregs.
脂质转移蛋白（LTPs）是存在于多种植物性食物中的过敏原。具体来说，桃的主要过敏原 Pru p 3 通常是引起严重过敏反应的原因。由于需要替代传统的食物过敏治疗方法，如限制性饮食，因此变应原免疫疗法作为一种很有前途的选择。已经证明，用含有甘露糖和 Pru p 3 肽的合成糖基化树突状肽，如 D1ManPrup3，进行舌下免疫疗法（SLIT）可诱导小鼠产生耐受，并且这种效应的持续存在取决于治疗剂量（2nM 或 5nM）。此外，它会产生与树突状细胞差异基因表达和甲基化谱相关的变化，以及调节性 T 细胞（Treg）的表型变化。然而，目前尚无研究工作探讨维持耐受反应的细胞亚群（Treg）中 DNA 甲基化变化的表观遗传变化。因此，在这项工作中，评估了 Pru p 3 过敏小鼠脾脏-Treg 中的 DNA 甲基化变化。
通过全基因组亚硫酸氢盐测序进行比较，比较 SLIT-D1ManPrup3 处理的小鼠：耐受（2nM D1ManPrup3）、脱敏（5nM D1ManPrup3）和未处理的致敏（仅抗原）与过敏小鼠。
大多数甲基化变化发生在 SLIT 处理的两组（脱敏组和耐受组）的基因启动子中，其次是仅抗原组（1,151 个）。尽管耐受和脱敏小鼠显示出相似数量的甲基化变化，但只有 445 个基因在两者中共享。值得注意的是，在 Treg 功能的关键转录因子如 、 、 、 、 和 的启动子区域观察到有趣的甲基化变化。事实上，仅在耐受组中观察到 被高度甲基化，而 仅在脱敏小鼠中被高度甲基化。
总之，不同剂量的 D1ManPrup3 在小鼠中诱导不同的反应（耐受或脱敏），这反映在 Treg 中的差异甲基化变化上。
