Epithelial Barrier Function in Respiratory Health

The respiratory epithelium forms a continuous lining from the nasal vestibule to the distal alveoli, acting as both a physical barricade against inhaled particles and a dynamic immunological interface. Intercellular junctional complexes, notably tight and adherens junctions, seal the paracellular space and regulate selective permeability. Overlying mucus, propelled by coordinated ciliary activity, traps and clears pathogens and allergens, while epithelial cells detect insults and release mediators that orchestrate local and systemic immune responses. Integrity of this barrier is essential for preventing tissue damage, infection and aberrant inflammation. Disruption of epithelial cohesion, altered mucus production and imbalanced repair processes are central to the pathogenesis of asthma, allergic rhinitis, chronic rhinosinusitis and susceptibility to viral or bacterial pneumonia. Advances in understanding molecular regulators of junctional assembly, epithelial‐immune crosstalk and barrier restoration have opened new avenues for biomarker discovery and targeted therapies designed to reinforce epithelial resilience and prevent disease progression.

Research from Nature Portfolio

Recent studies employing a lung‐specific deletion of the adherens junction protein E-cadherin have demonstrated that loss of cell–cell adhesion precipitates progressive epithelial denudation, goblet cell metaplasia and enlargement of alveolar spaces reminiscent of obstructive airway disease. These findings establish a causal link between E-cadherin–mediated junctional integrity and chronic airway inflammation, indicating that stabilisation of adherens junctions may represent a viable strategy for preventing barrier breakdown and downstream immune activation in conditions such as asthma.

Epithelial Barrier Function in Respiratory Health publication trend

The graph below shows the total number of articles in epithelial barrier function in respiratory health across all publications each year (not limited to Nature Index journals).

Technical terms

Tight junctions: Multiprotein complexes that seal adjacent epithelial cells, regulating paracellular transport and maintaining polarity.

Adherens junctions: Cadherin-based structures that provide mechanical adhesion between epithelial cells and link to the cytoskeleton.

Mucociliary clearance: Process by which mucus entrapping inhaled particles is transported out of the airways by coordinated ciliary beating.

Goblet cell metaplasia: Adaptive transformation of airway epithelial cells into mucus-secreting goblet cells, often in response to chronic inflammation.

E-cadherin: Transmembrane cadherin family protein central to adherens junctions and epithelial tissue integrity.

References

1. The airway epithelium: an orchestrator of inflammation, a key structural barrier and a therapeutic target in severe asthma. European Respiratory Journal (2024).
2. The epithelial era of asthma research: knowledge gaps and future direction for patient care. European Respiratory Review (2024).
3. Allergic Rhinitis: A Clinical and Pathophysiological Overview. Frontiers in Medicine (2022).
4. Interleukin-13 Alters Tight Junction Proteins Expression Thereby Compromising Barrier Function and Dampens Rhinovirus Induced Immune Responses in Nasal Epithelium. Frontiers in Cell and Developmental Biology (2020).
5. Characterization of a lung epithelium specific E-cadherin knock-out model: Implications for obstructive lung pathology. Scientific Reports (2018).