Neurons that produce the neurotransmitter dopamine communicate with T cells to enhance allergic inflammation in the lungs of young mice—but not older mice. The findings, published today in Immunity, could potentially explain why asthma susceptibility is higher in children than in adults. By highlighting the important role of interactions between the nervous system and the immune system in childhood asthma, the results could lead to new strategies for treating the common chronic disease.
The researchers discovered that sympathetic nerves innervating the mouse lung primarily produced dopamine in early postnatal life and norepinephrine in adult life. A similar pattern was evident when they compared lung and lymph node tissues from children up to 13 years of age and adults ranging in age from 40 to 65 years.
In addition, the researchers found that dopamine released by sympathetic nerves innervating the lung binds to the dopamine neurotransmitter receptor on CD4+ T helper cells to promote their differentiation into asthma-exacerbating Th2 cells, thereby enhancing lung inflammation. By contrast, norepinephrine-producing nerves in the adult lung had no such effect. Importantly, the findings reveal the similarity between mice and humans in terms of the innervation of dopamine-producing nerves in the early lung and the T cell response to dopamine.
In mouse models of allergen exposure, the dopamine-DRD4 pathway significantly increased Th2 cell inflammation in the lung tissue of neonatal mice, reducing mucus overproduction and airway hyper-responsiveness. By contrast, these effects were either not evident or much weaker in adult mice exposed to allergens.
Taken together, these findings demonstrate that the dopamine-DRD4 signaling between sympathetic nerves and CD4+ T helper cells in the lung plays an important role in augmenting allergic inflammation in early life. By facilitating inflammation, dopamine-producing nerves may endow the early lung with a mechanism of tissue repair following infection, which may be advantageous when the lung is immature and vulnerable to pathogens.
“We hope our findings can be used to facilitate the discovery of specific biomarkers for the identification of allergic asthma in children and to predict the severity and progression of the disease,” says senior author Xingbin Ai of Harvard. “In addition, targeting the communication between sympathetic nerves and CD4+ T cells via the dopamine-DRD4 pathway may be a strategy to battle the increasing prevalence of allergic asthma in children.”