Two Genes Expressed in Airway Epithelial Cells Play Important Roles in the Development of Asthma
Epithelial cells lining the airways are the first line of defense against infections and allergens, and doctors are increasingly understanding the role played by pulmonary immune responses - initiated early in development, in utero, and during infancy - in the development of asthma and other lung disorders.
Jeffrey Whitsett, MD, Co-Director of the Perinatal Institute, and a team of pulmonary biology researchers have shown that airway epithelial cells orchestrate immune responses after birth that influence subsequent allergic inflammation, leading to asthma.
Specifically, the researchers found that the genes SPDEF and FOXA3, which control mucus production and goblet cell differentiation, program pulmonary immune responses early in life and are sufficient and required to induce asthma. Goblet cells secrete the major components of mucus. The SDPEF and FOXA3 genes, expressed only in airway epithelial cells, control inflammatory responses to allergens and infections, programming subsequent asthma-like responses.
Whitsett’s study, which measured immune system responses in the lungs of neonatal mice, appeared May 4, 2015 in The Journal of Clinical Investigation. It concludes that exposure to commensal and pathogenic microbes and antigens influences goblet cells in the airways that determine the acquisition of immune responses after birth, responses that are likely to have long-term effects on the patterning of subsequent immune and inflammatory responses of the lung, leading to asthma.
“Inhibition of mucus cell hyperactivity induced by SPDEF following lung infections or exposure to allergies,” says Whitsett, “provides a novel, therapeutic approach for treatment and prevention of chronic airway diseases associated with excess mucus, including asthma and cystic fibrosis, common causes of severe lung disease in children.”
