Allergic asthma is the most chronic disease among children and can persist into adulthood. It is characterized by wheezing and breathing difficulties triggered by allergens such as pollen, mold, and pet dander. Now, researchers at Massachusetts General Hospital (MGH) have found in mice, how the relationship between nerves and immune cells in the lungs can contribute to the development of allergic asthma.
Their findings are published in the Journal of Allergy & Clinical Immunology in a paper titled, “Lung dopaminergic nerves facilitate the establishment of T helper 2 resident memory cells in early life,” and led by Xingbin Ai, PhD, an investigator at MGH and associate professor of pediatrics at Harvard Medical School.
“Allergic asthma develops from allergen exposure in early childhood and progresses into adulthood,” wrote the researchers. “The central mediator of progressive allergic asthma is allergen-specific, T helper 2 (Th2) resident memory cells (TRMs). Although the crosstalk between nerves and immune cells plays an established role in acute allergic inflammation, whether nerves facilitate the establishment of Th2-TRMs in the immature lung following early life allergen exposure is unknown.”
The work involved tracking allergen-specific immune cells called T helper 2 resident memory cells (Th2-TRMs) that are known to be the central mediator of recurrent allergic inflammation in the lungs.
Their experiments revealed that sympathetic nerves in the lungs produce dopamine and reside in proximity to certain T helper 2 cells following allergen exposure in newborns. When dopamine binds to DRD4 receptors on these T helper 2 cells, the cells are more prone to be transformed into Th2-TRMs and are instructed to produce immune response–stimulating molecules, or cytokines.
The researchers observed that blocking this dopamine binding following allergen exposure in newborns reduced the T helper 2 cell transformation and alleviated lung inflammation upon encountering the same allergen during adulthood.
“Since human lungs are similarly innervated by dopaminergic nerves in early postnatal life, the dopamine-DRD4 axis may provide a therapeutic target to modify allergic asthma progression from childhood to adulthood,” said Ai. “Dopamine signaling is likely one of many age-related factors that regulate Th2-TRMs in the immature lung. Moving forward, it will be important to further delineate the molecular and functional features of the pathogenic Th2-TRMs generated in the immature lung. A better understanding of the mediators of the early life Th2-TRM program could identify new therapeutic targets for the treatment of allergic asthma.”