Multifactorial Causes and Consequences of TLSP Production, Function, and Release in the Asthmatic Airway.

Disruption of the airway epithelium triggers a defensive immune response that begins with the production and release of alarmin cytokines. These epithelial-derived alarmin cytokines, including thymic stromal lymphopoietin (TSLP), are produced in response to aeroallergens, viruses, and toxic inhalants. An alarmin response disproportionate to the inhaled trigger can exacerbate airway diseases such as asthma.

The Genetic Factors of the Airway Epithelium Associated with the Pathology of Asthma.

Asthma is a chronic disease of the airways characterized by inflammation, tightened muscles, and thickened airway walls leading to symptoms such as shortness of breath, chest tightness, and cough in patients. The increased risk of asthma in children of asthmatics parents supports the existence of genetic factors involved in the pathogenesis of this disease. Genome-wide association studies have discovered several single nucleotide polymorphisms associated with asthma.

The Role of Airway Epithelial Cell Alarmins in Asthma.

The airway epithelium is the first line of defense for the lungs, detecting inhaled environmental threats through pattern recognition receptors expressed transmembrane or intracellularly. Activation of pattern recognition receptors triggers the release of alarmin cytokines IL-25, IL-33, and TSLP. These alarmins are important mediators of inflammation, with receptors widely expressed in structural cells as well as innate and adaptive immune cells.