Schaub Bianca, Liu Jing, Höppler Sabine, Schleich Isolde, Huehn Jochen, Olek Sven, Wieczorek Georg, Illi Sabina, von Mutius Erika
Department of Pulmonary and Allergy, University Children's Hospital Munich, LMU Munich, Munich, Germany.
J Allergy Clin Immunol. 2009 Apr;123(4):774-82.e5. doi: 10.1016/j.jaci.2009.01.056.
Cross-sectional studies suggest that maternal exposure to farming decreases the risk of allergic diseases in offspring. The potential underlying immunologic mechanisms are not understood.
We sought to assess whether maternal farm exposure activates regulatory T (Treg) cells in cord blood, exerting T(H)2-suppressive effects after microbial stimulation.
Eighty-four pregnant mothers were recruited before delivery. Detailed questionnaires (60 nonfarming and 22 farming mothers with 2 exclusions) assessed the farming exposures. Cord blood was stimulated with the microbial stimulus peptidoglycan (Ppg), the mitogen PHA, house dust mite extracts (Der p 1), and combinations. Treg cells (CD4+CD25(high) cells; intracellular forkhead/winged-helix family transcriptional repressor p3 [FOXP3] expression, FOXP3 levels, lymphocyte activation gene 3 mRNA expression, functional studies, and DNA methylation of the FOXP3 locus), proliferation, and T(H)2/T(H)1/T(H)17 cytokines were examined.
Cord blood Treg cell counts (both unstimulated and PHA stimulated) were increased with maternal farming exposures and associated with higher FOXP3 (Der p 1 + Ppg stimulation) and trendwise higher lymphocyte activation gene 3 (Ppg) expression. Furthermore, Treg cell function was more efficient with farming exposure (effector cell suppression, P = .004). In parallel, T(H)2 cytokine (IL-5) levels were decreased and associated with decreased lymphoproliferation and increased IL-6 levels (Ppg stimulation, Der p 1 + Ppg stimulation, or both; P < .05). Maternal exposure to increasing numbers of farm animals and stables was discovered to exert distinct effects on Treg cells, T(H)1/T(H)2 cells, or both. Additionally, FOXP3 demethylation in offspring of mothers with farm milk exposure was increased (P = .02).
Farm exposures during pregnancy increase the number and function of cord blood Treg cells associated with lower T(H)2 cytokine secretion and lymphocyte proliferation on innate exposure. One fascinating speculation is that maternal farm exposure might reflect a natural model of immunotherapy, potentially including a selection of innate stimuli in addition to allergen, shaping a child's immune system at an early stage.
横断面研究表明，母亲接触农业环境可降低后代患过敏性疾病的风险。但其潜在的免疫机制尚不清楚。
我们试图评估母亲在孕期接触农业环境是否会激活脐血中的调节性T（Treg）细胞，使其在受到微生物刺激后发挥抑制辅助性T2（Th2）细胞的作用。
在分娩前招募了84名孕妇。通过详细问卷（60名非农业接触者和22名农业接触者母亲，排除2例）评估农业接触情况。用微生物刺激物肽聚糖（Ppg）、丝裂原PHA、屋尘螨提取物（Der p 1）及其组合刺激脐血。检测Treg细胞（CD4+CD25（高表达）细胞；细胞内叉头/翼状螺旋家族转录抑制因子p3 [FOXP3]表达、FOXP3水平、淋巴细胞激活基因3 mRNA表达、功能研究以及FOXP3基因座的DNA甲基化）、增殖情况以及Th2/Th1/Th17细胞因子。
脐血Treg细胞计数（未刺激和PHA刺激后）随母亲农业接触情况增加而升高，且与更高的FOXP3（Der p 1 + Ppg刺激）以及呈上升趋势的更高的淋巴细胞激活基因3（Ppg刺激）表达相关。此外，农业接触使Treg细胞功能更有效（效应细胞抑制，P = 0.004）。同时，Th2细胞因子（IL-5）水平降低，且与淋巴细胞增殖减少和IL-6水平升高相关（Ppg刺激、Der p 1 + Ppg刺激或两者均有；P < 0.05）。发现母亲接触的农场动物和畜舍数量增加对Treg细胞、Th1/Th2细胞或两者均有不同影响。此外，母亲接触农场牛奶的后代中FOXP3去甲基化增加（P = 0.02）。
孕期接触农业环境可增加脐血Treg细胞的数量和功能，这与天然接触后较低的Th2细胞因子分泌和淋巴细胞增殖相关。一个引人入胜的推测是，母亲接触农业环境可能反映了一种免疫治疗的自然模式，可能除了过敏原外还包括对天然刺激物的选择，在早期塑造儿童的免疫系统。
