Brecht Steelant

Background: Airway basal cells are the progenitor cells within the airways and are capable of self-renewing and differentiating to multiple types of airway epithelial cells under steady-state and after injury (Ruysseveldt et al., Front. in Allergy, 2021). Recently, immune cells were shown to interact with basal cells, interfering with normal basal cell function, though this is not fully understood in upper airway diseases. Objective: To phenotypically compare the basal cell population of controls and patients with allergic rhinitis (AR) and to investigate their response to IL-4 and histamine. Methods: Primary nasal epithelial cells from controls and AR patients were isolated and basal cell populations were determined using scRNAseq. Sorted CD151 and CD142 double-positive basal cells were either cultured in air-liquid interface on transwell inserts or grown in culture plates and stimulated with IL-4 and histamine. Results: scRNAseq and flow cytometry revealed that AR patients have a higher fraction of histamine receptor 1 (H1R)-expressing basal cells compared to healthy controls (5.16% vs 2.49%, p = 0.0143). No differences for IL-4 receptor expression were found. Moreover, stimulation of basal cell cultures with IL-4 (1815 vs 288 W/cm2, p<0.001) and histamine (1824 vs 1040 W/cm2, p<0.05) resulted in lower trans-epithelial electrical resistance (TEER) during differentiation and slower wound closure after injury. Conclusion: IL-4 and histamine modulate basal cell function, delaying epithelial repair mechanisms, and basal cells from AR patients are more sensitive to histamine compared to controls. This might imply that basal cells serve as key regulators in maintaining epithelial barrier dysfunction.

The airway epithelium provides a critical barrier to the outside environment. When its integrity is impaired, epithelial cells and residing immune cells collaborate to exclude pathogens and to heal tissue damage. Healing is achieved through tissue-specific stem cells: the airway basal cells. Positioned near the basal membrane, airway basal cells sense and respond to changes in tissue health by initiating a pro-inflammatory response and tissue repair via complex crosstalks with nearby fibroblasts and specialized immune cells. In addition, basal cells have the capacity to learn from previous encounters with the environment. Inflammation can indeed imprint a certain memory on basal cells by epigenetic changes so that sensitized tissues may respond differently to future assaults and the epithelium becomes better equipped to respond faster and more robustly to barrier defects. This memory can, however, be lost in diseased states. In this review, we discuss airway basal cells in respiratory diseases, the communication network between airway basal cells and tissue-resident and/or recruited immune cells, and how basal cell adaptation to environmental triggers occurs.

Martens K, et al. Allergy Asthma Immunol Res. 2022 Jan;14(1):146-146. https://doi.org/10.4168/aair.2022.14.1.146

Taste receptors are well known for their role in the sensation of taste. Surprisingly, the expression and involvement of taste receptors in chemosensory processes outside the tongue have been recently identified in many organs including the airways. Currently, a clear understanding of the airway-specific function of these receptors and the endogenous activating/inhibitory ligands is lagging. The focus of this review is on recent physiological and clinical data describing the taste receptors in the airways and their activation by secreted bacterial compounds. Taste receptors in the airways are potentially involved in three different immune pathways (i.e., the production of nitric oxide and antimicrobial peptides secretion, modulation of ciliary beat frequency, and bronchial smooth muscle cell relaxation). Moreover, genetic polymorphisms in these receptors may alter the patients’ susceptibility to certain types of respiratory infections as well as to differential outcomes in patients with chronic inflammatory airway diseases such as chronic rhinosinusitis and asthma. A better understanding of the function of taste receptors in the airways may lead to the development of a novel class of therapeutic molecules that can stimulate airway mucosal immune responses and could treat patients with chronic airway diseases.

Adequate nasal breathing is indispensable for athletes, and nasal symptoms have been shown to interfere with their subjective feeling of comfortable breathing and quality of life. Nasal symptoms are caused by either structural abnormalities or mucosal pathology. Structural pathologies are managed differently from mucosal disease, and therefore, adequate diagnosis is of utmost importance in athletes in order to choose the correct treatment option for the individual. Literature suggests that nasal symptoms are more prevalent in athletes compared to the general population and certain sports environments might even trigger the development of symptoms. Given the high demands of respiratory function in athletes, insight into triggering factors is of high importance for disease prevention. Also, it has been suggested that athletes are more neglectful to their symptoms and hence remain undertreated, meaning that special attention should be paid to education of athletes and their caregivers. This review aims at giving an overview of nasal physiology in exercise as well as the possible types of nasal pathology. Additionally, diagnostic and treatment options are discussed and we focus on unmet needs for the management and prevention of these symptoms in athletes within the concept of precision medicine.

Martens K, et al. Allergy Asthma Immunol Res. 2021 Jul;13(4):560-575. https://doi.org/10.4168/aair.2021.13.4.560

Background: Staphylococcus aureus colonization and release of enterotoxin B (SEB) has been associated with severe chronic rhinosinusitis with nasal polyps (CRSwNP). The pathogenic mechanism of SEB on epithelial barriers, however, is largely unexplored.Objective: We investigated the effect of SEB on nasal epithelial barrier function.Methods: SEB was apically administered to air‐liquid interface (ALI) cultures of primary polyp and nasal epithelial cells of CRSwNP patients and healthy controls, respectively. Epithelial cell integrity and tight junction expression were evaluated. The involvement of Toll‐like receptor 2 (TLR2) activation was studied in vitro with TLR2 monoclonal antibodies and in vivo in tlr2^−/− knockout mice.Results: SEB applied to ALI cultures of polyp epithelial cells decreased epithelial cell integrity by diminishing occludin and zonula occludens (ZO)‐1 protein expression. Antagonizing TLR2 prevented SEB‐induced barrier disruption. SEB applied in the nose of control mice increased mucosal permeability and decreased mRNA expression of occludin and ZO‐1, whereas mucosal integrity and tight junction expression remained unaltered in tlr2^−/− mice. Furthermore, in vitro SEB stimulation resulted in epithelial production of IL‐6 and IL‐8, which was prevented by TLR2 antagonization.Conclusion & Clinical relevance: SEB damages nasal polyp epithelial cell integrity by triggering TLR2 in CRSwNP. Our results suggest that SEB might represent a driving factor of disease exacerbation, rather than a causal factor for epithelial defects in CRSwNP. Interfering with TLR2 triggering might provide a way to avoid the pathophysiological consequences of S. aureus on inflammation in CRSwNP.