Allergy Risk Is Mediated by Dendritic Cells with Congenital Epigenetic Changes
Allergy Risk Is Mediated by Dendritic Cells with Congenital Epigenetic Changes
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DOI：
10.1165/rcmb.2009-0400oc
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发表时间：
2011-03-01
影响因子：
6.4
通讯作者：
Kobzik, Lester
中科院分区：
文献类型：
--
作者：
Fedulov, Alexey V.;Kobzik, Lester
导致过敏反应的一个因素是母亲有过敏史。在母亲传播哮喘风险的小鼠模型中，哮喘的后代患有哮喘，但不正常，母亲表现出更高的过敏敏感性，在人类中重新进行了流行病学观察。树突状细胞(DC)捕获并处理抗原，并可使免疫反应向亲过敏的T辅助2表型倾斜。全基因组分析显示，过敏母亲的新生儿出生时脾CD11c(+)树突状细胞中的DNA甲基化发生了实质性变化，这些发现没有与任何过敏原接触。我们证明，这些来自哮喘母亲所生的未产生过敏原的新生儿的DC，而不是来自正常母亲的后代的DC，在过继转移到正常受体小鼠中时，对多种过敏原的过敏性易感性增加，表现为呼吸道反应性增加和过敏性炎症。其他免疫脾细胞，包括巨噬细胞和CD4+T细胞，没有传递这种效应。“哮喘易感”DC在体外也表现出更强的过敏原呈递活性。我们的发现表明，母体过敏会导致新生儿DC的表观遗传学改变，这种改变独立于与过敏原的接触，并与亲过敏功能有关。
One factor predisposing toward allergic responses is a maternal history of allergy. In a mouse model of maternal transmission of asthma risk, offspring of asthmatic, but not normal, mothers show increased allergic susceptibility, recreating epidemiologic observations in humans. Dendritic cells ( DCs) capture and process antigens, and can skew immune responses toward a pro-allergic T helper 2 phenotype. Genome-wide analysis shows that neonates of allergic mothers are born with substantial changes in DNA methylation in their splenic CD11c(+) DCs, findings observed without any contact with allergens. We demonstrate that these DCs from allergen-naive neonates born to asthmatic mothers, but not DCs from offspring of normal mothers, confer increased allergic susceptibility to multiple allergens when adoptively transferred into normal recipient mice, manifesting as increased airway responsiveness and allergic inflammation. Other immune splenocytes, including macrophages and CD4+ T cells, did not transfer the effect. The "asthma-susceptible" DCs also show enhanced allergen-presentation activity in vitro. Our findings suggest that maternal allergy results in an altered epigenetic profile in neonatal DCs that is independent of encounters with allergens and is linked to pro-allergic function.