The Role of Airway Epithelial Cell Alarmins in Asthma.
Christiane E WhetstoneMaral RanjbarHafsa OmerRuth P CusackGail M GauvreauPublished in: Cells (2022)
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. Many of the key effector cells in the allergic cascade also produce alarmins, thereby contributing to the airways disease by driving downstream type 2 inflammatory processes. Randomized controlled clinical trials have demonstrated benefit when blockade of TSLP and IL-33 were added to standard of care medications, suggesting these are important new targets for treatment of asthma. With genome-wide association studies demonstrating associations between single-nucleotide polymorphisms of the TSLP and IL-33 gene and risk of asthma, it will be important to understand which subsets of asthma patients will benefit most from anti-alarmin therapy.
Keyphrases
- chronic obstructive pulmonary disease
- allergic rhinitis
- lung function
- induced apoptosis
- clinical trial
- cystic fibrosis
- oxidative stress
- immune response
- end stage renal disease
- healthcare
- ejection fraction
- palliative care
- double blind
- prognostic factors
- peritoneal dialysis
- dendritic cells
- air pollution
- quality improvement
- signaling pathway
- bone marrow
- gene expression
- copy number
- regulatory t cells
- chronic pain
- transcription factor
- peripheral blood
- cell proliferation
- combination therapy