Epithelial Barrier Dysfunction in Chronic Respiratory Diseases

Abstract

Mucosal surfaces are lined by epithelial cells, which provide a complex and adaptive module that ensures first-line defense against external toxics, irritants, antigens, and pathogens. The underlying mechanisms of host protection encompass multiple physical, chemical, and immune pathways. In the lung, inhaled agents continually challenge the airway epithelial barrier, which is altered in chronic diseases such as chronic obstructive pulmonary disease, asthma, cystic fibrosis, or pulmonary fibrosis. In this review, we describe the epithelial barrier abnormalities that are observed in such disorders and summarize current knowledge on the mechanisms driving impaired barrier function, which could represent targets of future therapeutic approaches.

Keywords: COPD; airway epithelium; asthma; barrier dysfunction; cystic fibrosis; idiopathic pulmonary fibrosis; mucosal immunity.

FIGURE 1

Schematized view of main epithelial alterations observed in COPD, asthma, and cystic fibrosis as compared with a normal airway epithelium.

FIGURE 2

Schematized view of the main mechanisms driving airway epithelium alterations in chronic respiratory diseases. Arrows and boxes are colored depending on the condition or disease driving the represented dysfunctions. Red stands for CF-induced abnormalities, yellow for CS and COPD, green for viruses, brown for bacteria, and blue for airborne allergens and asthma-associated cytokine panels. (A) Mechanisms altering mucociliary clearance and mucus composition in chronic respiratory diseases. (B) Main factors driving goblet cell hyperplasia and decreased ciliated cell numbers and function. (C) Mechanisms driving impaired pIgR expression and d-IgA basoapical transcytosis. (D) Mechanisms of altered physical barrier dysfunction (tight and adherens junctions).