Young children are more susceptible to developing allergic asthma than adults. As neural innervation of the peripheral tissue continues to develop after birth, neurons may modulate tissue inflammation in an age-related manner. Here we showed that sympathetic nerves underwent a dopaminergic-to-adrenergic transition during post-natal development of the lung in mice and humans. Dopamine signaled through a specific dopamine receptor (DRD4) to promote T helper 2 (Th2) cell differentiation. The dopamine-DRD4 pathway acted synergistically with the cytokine IL-4 by upregulating IL-2-STAT5 signaling and reducing inhibitory histone trimethylation at Th2 gene loci. In murine models of allergen exposure, the dopamine-DRD4 pathway augmented Th2 inflammation in the lungs of young mice. However, this pathway operated marginally after sympathetic nerves became adrenergic in the adult lung. Taken together, the communication between dopaminergic nerves and CD4+ T cells provides an age-related mechanism underlying the susceptibility to allergic inflammation in the early lung.

中文翻译：

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年龄相关的多巴胺能神经增生T辅助物2型肺部过敏性炎症。

幼儿比成年人更容易患上过敏性哮喘。随着出生后周围组织的神经支配继续发展，神经元可能以与年龄相关的方式调节组织炎症。在这里，我们表明，在小鼠和人类的肺部出生后发育过程中，交感神经经历了多巴胺能向肾上腺素能的过渡。多巴胺通过特定的多巴胺受体（DRD4）发出信号，从而促进T辅助2（Th2）细胞分化。多巴胺-DRD4途径通过上调IL-2-STAT5信号传导并减少Th2基因位点的抑制性组蛋白三甲基化而与细胞因子IL-4协同作用。在过敏原暴露的小鼠模型中，多巴胺-DRD4途径增强了幼鼠肺部的Th2炎症。然而，在成年肺交感神经变成肾上腺素能后，该途径微弱地起作用。综上所述，多巴胺能神经与CD4 + T细胞之间的交流提供了一种与年龄相关的机制，该机制是早期肺部对过敏性炎症的易感性的基础。