Plasmacytoid dendritic cell deficiency in neonates enhances allergic airway inflammation via reduced production of IFN-alpha
Plasmacytoid dendritic cell deficiency in neonates enhances allergic airway inflammation via reduced production of IFN-alpha
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新生儿浆细胞样树突状细胞缺陷通过减少 IFN-α 的产生而增强过敏性气道炎症
DOI：
10.1038/s41423-019-0333-y
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发表时间：
2020
影响因子：
24.1
通讯作者：
Han Junyan
中科院分区：
文献类型：
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作者：
Wu Min;Gao Liuchuang;He Miao;Liu Hangyu;Jiang Han;Shi Ketai;Shang Runshi;Liu Bing;Gao Shan;Chen Hebin;Gong Feili;Gelf;Erwin W.;Huang Yafei;Han Junyan
过敏性哮喘是一种与2型细胞因子相关的慢性炎症性气道疾病，通常起源于生命早期。早期的免疫应答表现出Th 2细胞偏好，但确切的机制仍然难以捉摸。在过敏性哮喘中起调节作用的浆细胞样树突状细胞（pDC）在新生小鼠中显示出缺陷。我们在此报道，在OVA诱导的实验性哮喘模型中，这种pDC缺乏使新生小鼠比成年小鼠更容易发生严重的过敏性气道炎症。pDC的连续转移或IFN-α给药可预防野生型小鼠过敏性炎症的发生，但在IFNAR 1 −/−小鼠中则不然。类似地，当pDC耗尽时，成年小鼠发展更严重的过敏性炎症。pDC的保护作用是通过pDC-/IFN-α介导的对上皮细胞来源的CCL 20、GM-CSF和IL-33分泌的负调节介导的，这反过来又损害了cDC 2和ILC 2细胞向气道的募集。在哮喘患者中，儿童pDC的百分比和IFN-α的水平低于成人。这些结果表明，在新生儿的pDC-上皮细胞串扰的损害是过敏原诱导的过敏性气道炎症的发展的易感因素。
Allergic asthma, a chronic inflammatory airway disease associated with type 2 cytokines, often originates in early life. Immune responses at an early age exhibit a Th2 cell bias, but the precise mechanisms remain elusive. Plasmacytoid dendritic cells (pDCs), which play a regulatory role in allergic asthma, were shown to be deficient in neonatal mice. We report here that this pDC deficiency renders neonatal mice more susceptible to severe allergic airway inflammation than adult mice in an OVA-induced experimental asthma model. Adoptive transfer of pDCs or administration of IFN-α to neonatal mice prevented the development of allergic inflammation in wild type but not in IFNAR1−/−mice. Similarly, adult mice developed more severe allergic inflammation when pDCs were depleted. The protective effects of pDCs were mediated by the pDC-/IFN-α-mediated negative regulation of the secretion of epithelial cell-derived CCL20, GM-CSF, and IL-33, which in turn impaired the recruitment of cDC2 and ILC2 cells to the airway. In asthmatic patients, the percentage of pDCs and the level of IFN-α were lower in children than in adults. These results indicate that impairment of pDC-epithelial cell crosstalk in neonates is a susceptibility factor for the development of allergen-induced allergic airway inflammation.