Neonatal immune responses to TLR2 stimulation: influence of maternal atopy on Foxp3 and IL-10 expression.
Neonatal immune responses to TLR2 stimulation: influence of maternal atopy on Foxp3 and IL-10 expression.
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DOI：
10.1186/1465-9921-7-40
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发表时间：
2006-03-21
影响因子：
5.8
通讯作者：
Finn PW
中科院分区：
文献类型：
--
作者：
Schaub B;Campo M;He H;Perkins D;Gillman MW;Gold DR;Weiss S;Lieberman E;Finn PW
母体特应性背景和过敏原对适应性免疫系统的刺激在过敏性疾病的发展中相互作用。通过微生物暴露刺激先天免疫系统，如激活先天Toll样受体2(TLR2)，可能会减少儿童过敏的发展。然而，关于微生物刺激对早期免疫反应的免疫学影响以及与母体特应性的关系，人们知之甚少。我们分析了50名健康新生儿(31名非特应性和19名特应性母亲)脐血单个核细胞(CBMC)的免疫反应。用TLR2激动剂肽聚糖(Ppg)或变应原粉尘螨(Derf1)刺激细胞，并将结果与未刺激的细胞进行比较。分析CBMC的淋巴细胞增殖和细胞因子分泌情况。此外，我们还评估了与T调节细胞相关的基因表达，包括转录因子Foxp3、糖皮质激素诱导的肿瘤坏死因子受体(GITR)和细胞毒性淋巴细胞抗原4(CTLA4)。用3 H-胸腺嘧啶核苷掺入法检测淋巴细胞增殖反应，用ELISA法测定细胞因子浓度，用实时荧光定量RT-PCR法检测T细胞标志物的mRNA表达。PPG刺激主要诱导IL-10细胞因子的产生，此外还有干扰素-γ、IL-13和肿瘤坏死因子-α的分泌。刺激PPG后，GITR增加(p=0.07)。PPG诱导的IL-10的产生和Foxp3的诱导在无特应性的CBMC中高于有母体特应性的CBMC(p=0.04，p=0.049)。IL-10的产生与Foxp3(r=0.53，p=0.001)、GITR(r=0.47，p=0.004)和CTLA4(r=0.49，p=0.003)的表达呈高度正相关，与母体特应性无关。用ppg刺激TLR2诱导IL-10和与T调节细胞相关的基因，受母体特应性的影响。与特应性母亲相比，非特应性母亲CBMC中IL-10和Foxp3的诱导增加，可能表明对微生物刺激的反应能力增强。
Maternal atopic background and stimulation of the adaptive immune system with allergen interact in the development of allergic disease. Stimulation of the innate immune system through microbial exposure, such as activation of the innate Toll-like-receptor 2 (TLR2), may reduce the development of allergy in childhood. However, little is known about the immunological effects of microbial stimulation on early immune responses and in association with maternal atopy. We analyzed immune responses of cord blood mononuclear cells (CBMC) from 50 healthy neonates (31 non-atopic and 19 atopic mothers). Cells were stimulated with the TLR2 agonist peptidoglycan (Ppg) or the allergen house dust mite Dermatophagoides farinae (Derf1), and results compared to unstimulated cells. We analyzed lymphocyte proliferation and cytokine secretion of CBMC. In addition, we assessed gene expression associated with T regulatory cells including the transcription factor Foxp3, the glucocorticoid-induced TNF receptor (GITR), and the cytotoxic lymphocyte antigen 4 (CTLA4). Lymphocyte proliferation was measured by 3H-Thymidine uptake, cytokine concentrations determined by ELISA, mRNA expression of T cell markers by real-time RT-PCR. Ppg stimulation induced primarily IL-10 cytokine production, in addition to IFN-γ, IL-13 and TNF-α secretion. GITR was increased following Ppg stimulation (p = 0.07). Ppg-induced IL-10 production and induction of Foxp3 were higher in CBMC without, than with maternal atopy (p = 0.04, p = 0.049). IL-10 production was highly correlated with increased expression of Foxp3 (r = 0.53, p = 0.001), GITR (r = 0.47, p = 0.004) and CTLA4 (r = 0.49, p = 0.003), independent of maternal atopy. TLR2 stimulation with Ppg induces IL-10 and genes associated with T regulatory cells, influenced by maternal atopy. Increased IL-10 and Foxp3 induction in CBMC of non-atopic compared to atopic mothers, may indicate an increased capacity to respond to microbial stimuli.
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影响因子：
8.6
作者：
Gerosa, F;Nisii, C;Trinchieri, G
通讯作者：
Trinchieri, G
影响因子：
4.4
作者：
Sabroe, I;Jones, EC;Dower, SK
通讯作者：
Dower, SK
影响因子：
7
作者：
Gibson, UEM;Heid, CA;Williams, PM
通讯作者：
Williams, PM
影响因子：
7
作者：
Heid, CA;Stevens, J;Williams, PM
通讯作者：
Williams, PM
影响因子：
56.9
作者：
Pasare, C;Medzhitov, R
通讯作者：
Medzhitov, R