The epithelium is a layer of cells that forms a protective lining over various body surfaces. In the respiratory system, the airway epithelium lines the passages air travels through, from the nasal cavity to the smaller bronchioles. This cellular layer acts as a primary interface between the body and the external environment, maintaining the respiratory tract’s integrity and health.
The Airway Epithelium’s Normal Role
The airway epithelium functions as a physical barrier, protecting underlying tissues from inhaled particles, allergens, and microorganisms. This barrier is maintained by specialized cell-to-cell connections, like tight junctions, which seal spaces between epithelial cells. It also participates in mucociliary clearance, a process involving mucus and tiny hair-like structures called cilia.
Goblet cells within the epithelium produce mucus, a sticky substance that traps inhaled debris and pathogens. Ciliated cells rhythmically beat their cilia, moving the mucus layer upwards towards the throat for swallowing or expulsion. This cleansing mechanism helps prevent infections and irritation. Beyond physical defense, the epithelium secretes various defensive molecules, including antimicrobial peptides, protecting the airways.
Epithelial Dysfunction in Asthma
In individuals with asthma, the airway epithelium undergoes significant changes, leading to dysfunction. A common feature is epithelial damage or shedding, compromising the protective layer’s integrity. This damage increases permeability, allowing allergens, irritants, and pathogens to more easily penetrate the epithelial barrier and reach underlying tissues.
The altered epithelium in asthma also exhibits changes in gene expression, influencing its function and response to environmental triggers. For instance, reduced expression of cell-to-cell adhesion molecules like E-cadherin further weakens the barrier. This impaired barrier function is a consistent feature in asthma. Epithelial cells in asthmatic airways can also become activated, releasing specific cytokines such as thymic stromal lymphopoietin (TSLP), interleukin-25 (IL-25), and interleukin-33 (IL-33). These mediators contribute to the inflammatory environment characteristic of asthma.
How Epithelial Changes Drive Asthma Symptoms
The impaired epithelial barrier in asthma directly contributes to the condition’s characteristic symptoms. When compromised, allergens like dust mites or pollen, and irritants such as pollutants, can more readily pass through the epithelial layer. This increased penetration allows these substances to interact with immune cells beneath the epithelium, triggering a heightened inflammatory response in the airways.
Dysfunctional epithelial cells also release inflammatory mediators, including cytokines and chemokines, contributing to airway hyperresponsiveness. This manifests as exaggerated airway narrowing, or bronchoconstriction, in response to triggers that would not affect healthy individuals. These mediators can also stimulate increased mucus production by goblet cells, leading to excessive phlegm and congestion. Over time, repeated epithelial injury and repair can contribute to airway remodeling, involving thickening of the airway wall and increased deposition of extracellular matrix proteins.
Therapeutic Implications
Understanding the complex role of the epithelium in asthma has significantly influenced current treatment strategies and research. Therapies now aim not only to manage symptoms but also to address underlying epithelial dysfunction. For example, some treatments reduce inflammation within the epithelial layer, helping restore its protective capabilities.
Approaches are also exploring ways to directly enhance or repair epithelial barrier function. This could involve targeting specific molecules responsible for maintaining cell-to-cell connections or promoting healthy epithelial cell regeneration. Such strategies seek to modify the disease’s progression by strengthening the airway’s first line of defense.