Department of Pediatrics, National Jewish Health, Denver, Colo.
Department of Medicine, University of Colorado School of Medicine, Aurora, Colo; Center for Genes, Environment, and Health, National Jewish Health, Denver, Colo.
J Allergy Clin Immunol. 2018 Feb;141(2):659-670.e2. doi: 10.1016/j.jaci.2017.04.020. Epub 2017 May 4.
Regulatory T (Treg) cells play an essential role in the maintenance of immune homeostasis in allergic diseases.
We sought to define the mechanisms underlying induction of tolerance to peanut protein and prevention of the development of peanut allergy.
High or low doses of peanut extract were administered to pups every day for 2 weeks before peanut sensitization and challenge. After challenge, symptoms, Treg cell numbers, and forkhead box protein 3 (Foxp3), T2 and T17 cytokine, and Tgfβ expression in mesenteric lymph node (MLN) CD4 T cells and jejunum were monitored. Treg cell suppressive activity and Foxp3 methylation in MLN CD4 T cells were assayed.
Feeding high but not low doses of peanut before sensitization induced tolerance, as demonstrated by prevention of diarrhea and peanut-specific IgE responses, increases in the percentage of CD4CD25FoxP3 cells in MLNs, and Foxp3 mRNA and protein expression in CD4 cells from MLNs or jejunum. Feeding high doses of peanut before sensitization decreased percentages of CD3CD4IL-13 and CD3CD4IL-17 cells in MLNs and decreased Il13 and Il17a and increased Tgfβ mRNA expression in the jejunum; numbers of CD103 dendritic cells in MLNs were significantly increased. Treg cell suppression was shown to be antigen specific. Foxp3 methylation was increased in peanut extract-sensitized and challenged mice, whereas in tolerized mice levels were significantly reduced.
Feeding high doses of peanut to pups induced tolerance to peanut protein. Foxp3 demethylation was associated with tolerance induction, indicating that Treg cells play an important role in the regulation of peanut sensitivity and maintenance of immune homeostasis.
调节性 T（Treg）细胞在过敏性疾病的免疫稳态维持中起着至关重要的作用。
我们旨在确定诱导花生蛋白耐受和预防花生过敏发展的机制。
在花生致敏和激发前，每天给幼崽高或低剂量的花生提取物 2 周。激发后，监测症状、Treg 细胞数量、肠系膜淋巴结（MLN）CD4 T 细胞中的叉头框蛋白 3（Foxp3）、T2 和 T17 细胞因子以及 Tgfβ表达，以及空肠。检测 MLN CD4 T 细胞中的 Treg 细胞抑制活性和 Foxp3 甲基化。
在致敏前给予高剂量而不是低剂量的花生可诱导耐受，表现为预防腹泻和花生特异性 IgE 反应、MLN 中 CD4CD25FoxP3 细胞的百分比增加，以及 MLN 或空肠中 CD4 细胞的 Foxp3 mRNA 和蛋白表达增加。在致敏前给予高剂量的花生可减少 MLN 中 CD3CD4IL-13 和 CD3CD4IL-17 细胞的百分比，并减少 Il13 和 Il17a ，增加空肠中的 Tgfβ mRNA 表达；MLN 中 CD103 树突状细胞的数量显著增加。显示 Treg 细胞抑制具有抗原特异性。Foxp3 去甲基化与诱导耐受相关，表明 Treg 细胞在调节花生敏感性和维持免疫稳态方面发挥重要作用。
