Abstract
As neural innervation of the peripheral tissue continues to develop after birth, neurons may modulate tissue inflammation in an age-related manner. Herein, we investigated the role of the developing nervous system in the asthma diathesis that characterizes the early age. We showed that sympathetic nerves in the lung underwent a dopaminergic-to-adrenergic transition during postnatal development. In addition, dopamine was found to promote a T helper 2 (Th2) phenotype by signaling through a specific DRD4 receptor on CD4+ T cells. Mechanistically, the dopamine-DRD4 pathway acted synergistically with interleukin 4 (IL-4) by upregulating IL-2/STAT5 signaling and reducing inhibitory histone trimethylation at Th2 gene loci. Furthermore, in murine models of allergen exposure, we demonstrated that the dopamine-DRD4 pathway significantly augmented Th2 inflammation in the early lung, but much less so in the adult lung. Taken together, an age-related communication between dopaminergic nerves and CD4+ T cells augments Th2 inflammation in the early lung.
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