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.

中文翻译：

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新生儿的浆细胞样树突状细胞缺乏症通过减少IFN-α的产生而增强了过敏性气道炎症。

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，通常起源于早期生活。早期的免疫反应表现出Th2细胞偏倚，但确切的机制仍然难以捉摸。浆细胞样树突状细胞（pDC）在变应性哮喘中起调节作用，已被证明在新生小鼠中缺乏。我们在这里报告说，这种pDC缺乏症使新生小鼠比OVA诱发的实验性哮喘模型中的成年小鼠更容易受到严重的过敏性气道炎症的影响。pDC的过继转移或对新生小鼠的IFN-α给药可防止野生型变态反应性炎症的发展，但在IFNAR1-/-小鼠中则不能。同样，pDC耗尽时，成年小鼠会出现更严重的过敏性炎症。pDC的保护作用是由pDC- /IFN-α介导的上皮细胞源性CCL20，GM-CSF和IL-33分泌的负调节介导的，进而损害了cDC2和ILC2细胞对SDC的募集气道。在哮喘患者中，儿童的pDCs百分比和IFN-α水平低于成人。这些结果表明，新生儿pDC-上皮细胞串扰的损害是过敏原诱发的过敏性气道炎症发展的易感性因素。