Food antigens drive spontaneous IgE elevation in the absence of commensal microbiota
Food antigens drive spontaneous IgE elevation in the absence of commensal microbiota
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DOI：
10.1126/sciadv.aaw1507
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发表时间：
2019-05-01
期刊：
影响因子：
13.6
通讯作者：
Kim, Kwang Soon
中科院分区：
文献类型：
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作者：
Hong, Sung-Wook;Eunju, O.;Kim, Kwang Soon
免疫球蛋白E（IgE）是过敏性疾病的关键介质，在肠道微生物群受损的小鼠（如无菌（GF）和经抗过敏药物治疗的小鼠）中自发升高。然而，异常IgE升高的潜在机制仍不清楚。在这里，我们证明了食物抗原驱动自发IgE升高GF和抗肿瘤治疗的小鼠产生T辅助2（T（H）2）-歪斜的T滤泡辅助（T-FH）细胞在肠道相关淋巴组织（GALT）。在这些小鼠中，剥夺与食物抗原的接触导致有缺陷的IgE升高以及GALT中T-FH细胞和IgE产生细胞的产生受损。GF小鼠中食物抗原驱动的T-FH细胞主要在生命早期产生，特别是在断奶期间。我们还揭示了GF小鼠中食物抗原驱动的T-FH细胞通过肠道微生物群的定殖而被主动耗尽。因此，我们的研究结果为为什么早期生活中肠道微生物群的扰动会增加过敏性疾病的发生提供了可能的解释。
Immunoglobulin E (IgE), a key mediator in allergic diseases, is spontaneously elevated in mice with disrupted commensal microbiota such as germ-free (GF) and antibiotics-treated mice. However, the underlying mechanisms for aberrant IgE elevation are still unclear. Here, we demonstrate that food antigens drive spontaneous IgE elevation in GF and antibiotics-treated mice by generating T helper 2 (T(H)2)-skewed T follicular helper (T-FH) cells in gut-associated lymphoid tissues (GALTs). In these mice, depriving contact with food antigens results in defective IgE elevation as well as impaired generation of T-FH cells and IgE-producing cells in GALT. Food antigen-driven T-FH cells in GF mice are mostly generated in early life, especially during the weaning period. We also reveal that food antigen-driven T-FH cells in GF mice are actively depleted by colonization with commensal microbiota. Thus, our findings provide a possible explanation for why the perturbation of commensal microbiota in early life increases the occurrence of allergic diseases.