Asthma: a New Approach to the Bronchial Epithelium

Abstract

The bronchial epithelium serves as a critical defense line against environmental insults, acting not merely as a barrier but as a complex, dynamic system enriched with diverse cell types such as ciliated cells, goblet cells, and basal cells. Recent advancements in single-cell ribonucleic acid (RNA) sequencing have further unveiled the complexity of this layer by identifying additional cell types like ionocytes, neuroendocrine cells, tuft cells, deuterosomal cells, club cells and mucus ciliated cells. These cells collectively maintain respiratory health through various mechanisms including the mucociliary escalator, mucus production, airway repair, and immune modulation. Disruptions in the epithelial barrier can lead to respiratory diseases like asthma, highlighting the importance of understanding these intricate cellular relationships for developing targeted therapies. This epithelial complexity is crucial for pulmonary homeostasis and the pathogenesis of asthma, where abnormal epithelial remodeling and dysfunction are central. The identification of a novel mucous ciliated cell state in asthma, co-expressing genes associated with both ciliated and goblet cells, offers new insights into the disease’s pathogenesis and therapeutic targets. The epithelial barrier’s integrity, maintained by tight junctions and adherents’ junctions, is essential for protecting the underlying tissue from environmental threats. However, in asthma, this barrier is compromised, leading to increased allergen permeability, airway hyperresponsiveness, inflammation, and remodeling. Despite advances, the need for novel concepts in asthma pathogenesis remains, particularly to address the limitations of the current T helper 2-dominant paradigm in explaining the connection between airway inflammation and remodeling. Understanding the molecular mechanisms underlying epithelial barrier dysfunction could pave the way for novel asthma treatments focused on enhancing barrier integrity, ultimately improving patient outcomes.