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Asthma is a chronic respiratory condition predominantly driven by a type 2 immune response. Epithelial-derived alarmins such as thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, and IL-25 orchestrate the activation of downstream Th2 cells and group 2 innate lymphoid cells (ILC2s), along with other immune effector cells. While these alarmins are produced in response to inhaled triggers, such as allergens, respiratory pathogens or particulate matter, disproportionate alarmin production by airway epithelial cells can lead to asthma exacerbations. With alarmins produced upstream of the type 2 inflammatory cascade, understanding the pathways by which these alarmins are regulated and expressed is critical to further explore new therapeutics for the treatment of asthmatic patients. This review emphasizes the critical role of airway epithelium and epithelial-derived alarmins in asthma pathogenesis and highlights the potential of targeting alarmins as a promising therapeutic to improve outcomes for asthma patients. [ABSTRACT FROM AUTHOR]

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. Allergens inhaled into previously sensitized airways are known to drive a T2 inflammatory response through the polarization of T cells by dendritic cells mediated by TSLP. Harmful compounds found within air pollution, microbes, and viruses are also triggers causing airway epithelial cell release of TSLP in asthmatic airways. The release of TSLP leads to the development of inflammation which, when unchecked, can result in asthma exacerbations. Genetic and inheritable factors can contribute to the variable expression of TSLP and the risk and severity of asthma. This paper will review the various triggers and consequences of TSLP release in asthmatic airways. [ABSTRACT FROM AUTHOR]