研究发现年龄相关的肺炎机制

研究发现年龄相关的肺炎机制 作者： 发布时间：2019/11/20 14:26:56 美国波士顿布莱根妇女医院Xingbin Ai小组研究发现，与年龄相关的多巴胺能神经支配可增强后天肺中T辅助2（Th2）过敏性炎症反应。相关论文发表在11月19日的《免疫》杂志上。

他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。但是，在成年肺交感神经变成肾上腺素能后，该途径的作用很小。

综上所述，多巴胺能神经与CD4 + T细胞之间的通讯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敏感性的基础。

据了解，幼儿比成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，神经元可能以年龄相关的方式调节组织炎症。

附：英文原文

Title: Age-Related Dopaminergic Innervation Augments T Helper 2-Type Allergic Inflammation in the Postnatal Lung

Author: Wei Wang, Jonathan A. Cohen, Antonia Wallrapp, Kenneth G. Trieu, Juliana Barrios, Fengzhi Shao, Nandini Krishnamoorthy, Vijay K. Kuchroo, Matthew R. Jones, Alan Fine, Yan Bai, Xingbin Ai

Issue Volume: November 19, 2019

Abstract: 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.

DOI: 10.1016/j.immuni.2019.10.002

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Immunity：《免疫》，创刊于1994年。隶属于细胞出版社，最新if：21.522

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