Neonatal Immune State Is Influenced by Maternal Allergic Rhinitis and Associated With Regulatory T cells.
Neonatal Immune State Is Influenced by Maternal Allergic Rhinitis and Associated With Regulatory T cells.
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新生儿免疫状态受母体过敏性鼻炎影响并与调节性 T 细胞相关
DOI：
10.4168/aair.2017.9.2.133
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Tan L;Ou J;Tao Z;Kong Y;Xu Y
母亲的影响有助于过敏性疾病的起源，但其机制尚不清楚。目前的文献提示表观遗传学在过敏性疾病的发展中的作用。本研究旨在探讨调节性T（Treg）细胞和叉头盒p3（Foxp 3）DNA甲基化在变应性鼻炎（AR）易感性母体传递过程中的作用。在第1天和第7天，通过腹腔注射屋尘螨（Dermatophagoides pteronyssinus，Der p）1致敏BALB/c雌性小鼠（AR母体）。然后在第8天与正常的雄性小鼠交配。从第21天到第28天，用Der p 1连续鼻内攻击雌性小鼠。正常对照组同样给予生理盐水。于出生后第3天处死雌性小鼠及其子代，检测其鼻粘膜组织病理学、母鼠血清和子代脾脏匀浆中细胞因子、Treg细胞计数、Foxp 3 mRNA表达和脾脏Foxp 3 DNA甲基化水平。与正常对照组相比，Der p 1刺激的雌性小鼠新生仔鼠（AR仔鼠）脾匀浆中IL-4、IL-17水平升高（P <0.01），IL-10水平升高（P <0.01）。AR子代Treg细胞数明显低于正常子代（P<0.01）。AR子代与正常对照子代Foxp 3 DNA甲基化水平差异不明显，但相关分析显示，子代与母体Foxp 3 DNA甲基化水平之间存在显著正相关（r=0.803，P<0.01）。在母体AR的影响下，其新生后代发展为辅助性T细胞2型（Th 2）优势免疫状态，这与Treg细胞的衰退密切相关。Foxp 3 DNA甲基化可能是导致这种母体效应的一种机制，但仍需要更多的研究来确保。
Maternal influences contribute to the origin of allergic diseases, but the mechanisms are not clear. The current literature prompted the role of epigenetics in the development of allergic diseases. We sought to investigate the roles of regulatory T (Treg) cells and Forkhead box p3 (Foxp3) DNA methylation in the process of maternal transmission of allergic rhinitis (AR) susceptibility. BALB/c female mice (AR mother) were sensitized by intraperitoneal injection of Dermatophagoides pteronyssinus (Der p) 1 on day 1 and 7. Then they mated with normal male mice on day 8. From day 21 to 28, the female mice were intranasal challenged with Der p 1 continuously. The normal controls were given with normal saline in the same way. On postnatal day 3, Female mice and their offspring were sacrificed to detect their histopathology in nasal mucosae, cytokines in sera of mother and spleen homogenates of offspring, Treg cells count, Foxp3 mRNA expressions, and Foxp3 DNA methylation levels in spleens. Compared with the normal controls, neonatal offspring of Der p 1-stimulated female mice (AR offspring) showed the elevation of interleukin (IL)-4 (P<0.01) and IL-17 (P<0.01), the submission of IL-10 (P<0.01) in spleen homogenates. Further, Treg cells count in AR offspring decreased remarkably compared with the normal offspring (P<0.01). Though the difference of Foxp3 DNA methylation level between AR offspring and normal control offspring was not obvious, correlation analysis demonstrated that there was significantly positive correlation between Foxp3 DNA methylation level of mother and that of offspring (r=0.803, P<0.01). Under the influence of Maternal AR, their neonatal offspring develop into T-helper type 2 (Th2) dominant immune state, which is closely associated with the recession of Treg cells. Foxp3 DNA methylation may be a mechanism responsible for that maternal effect but still need more studies to ensure.