Topical Collection "Immunologic and Non-immunologic Mechanisms Leading to Airway Remodeling in Asthma"
Prof. Dr. Michael Roth
Pneumology, University Hospital Basel & Pulmonary Cell Research, Department Biomedicine, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
tissue remodeling in chronic lung diseases; asthma; COPD; lung fibrosis; epi-genetics; cell signaling; cell differentiation; epithelial cells; fibroblasts; airway smooth muscle cells
Special Issues and Collections in MDPI journals
Topical Collection Information
Airway wall remodeling is a frequent pathology in asthma which, currently, can only be treated by bronchial thermoplasty. Remodeling narrows the airway lumen, limiting airflow, and reduces the tissue’s flexibility, thereby slowing muscle relaxation. Neither anti-inflammatory drugs nor bronchodilators have any effect on tissue remodeling structural changes. Thus, it seems unlikely that inflammation is the only cause of remodeling. The origin of airway wall remodeling is not well understood, and it is unclear whether remodeling occurs in the same way in all asthma patients. The classic meaning of remodeling involves hyperplasia and hypertrophy of the airway smooth muscle bundle, but these may not be the only factors involved. It is therefore necessary to determine the mechanisms that increase the thickness of the sub-epithelial basal membrane. In addition, the following questions are of interest: What changes the composition of the airway’s extracellular matrix? Why do myo-fibroblasts increase? Recent studies suggest that epigenetic events are the key to understanding asthma and airway wall remodeling. These epigenetic modifications can be handed down over 2–3 generations and pre-dispose the next generation to chronic inflammatory lung diseases.
This collection aims to provide studies to improve the understand of (i) how different asthma triggers (allergic and non-allergic) may activate the same mechanism(s) leading to remodeling and (ii) if there are data that suggest different types of airway wall remodeling.
Prof. Dr. Michael Roth
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- Asthma associated airway wall remodeling
- Disease or triggers of specific types of airway wall remodeling
- Allergic and non-allergic triggers of remodeling
- Epigenetic mechanisms of remodeling
Published Papers (3 papers)
Der f 38 Is a Novel TLR4-Binding Allergen Related to Allergy Pathogenesis from Dermatophagoides farinae
Viewed by 849
It is difficult to treat allergic diseases including asthma completely because its pathogenesis remains unclear. House dust mite (HDM) is a critical allergen and Toll-like receptor (TLR) 4 is a member of the toll-like receptor family, which plays an important role in allergic
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It is difficult to treat allergic diseases including asthma completely because its pathogenesis remains unclear. House dust mite (HDM) is a critical allergen and Toll-like receptor (TLR) 4 is a member of the toll-like receptor family, which plays an important role in allergic diseases. The purpose of this study was to characterize a novel allergen, Der f 38 binding to TLR4, and unveil its role as an inducer of allergy. Der f 38 expression was detected in the body and feces of Dermatophagoides farinae
(DF). Electron microscopy revealed that it was located in the granule layer, the epithelium layer, and microvilli of the posterior midgut. The skin prick test showed that 60% of allergic subjects were Der f 38-positive. Der f 38 enhanced surface 203c expression in basophils of Der f 38-positive allergic subjects. By analysis of the model structure of Der p 38, the expected epitope sites are exposed on the exterior side. In animal experiments, Der f 38 triggered an infiltration of inflammatory cells. Intranasal (IN) administration of Der f 38 increased neutrophils in the lung. Intraperitoneal (IP) and IN injections of Der f 38 induced both eosinophils and neutrophils. Increased total IgE level and histopathological features were found in BALB/c mice treated with Der f 38 by IP and IN injections. TLR4 knockout (KO) BALB/c mice exhibited less inflammation and IgE level in the sera compared to wild type (WT) mice. Der f 38 directly binds to TLR4 using biolayer interferometry. Der f 38 suppressed the apoptosis of neutrophils and eosinophils by downregulating proteins in the proapoptotic pathway including caspase 9, caspase 3, and BAX and upregulating proteins in the anti-apoptotic pathway including BCL-2 and MCL-1. These findings might shed light on the pathogenic mechanisms of allergy to HDM.
Advances in the Knowledge of the Underlying Airway Remodeling Mechanisms in Chronic Rhinosinusitis Based on the Endotypes: A Review
Cited by 2
| Viewed by 941
Chronic rhinosinusitis (CRS) is a chronic inflammatory condition of the nasal and paranasal sinus mucosa that affects up to 10% of the population worldwide. CRS is the most representative disease of the upper respiratory tract where airway remodeling occurs, including epithelial damage, thickening
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Chronic rhinosinusitis (CRS) is a chronic inflammatory condition of the nasal and paranasal sinus mucosa that affects up to 10% of the population worldwide. CRS is the most representative disease of the upper respiratory tract where airway remodeling occurs, including epithelial damage, thickening of the basement membrane, fibrosis, goblet cell hyperplasia, subepithelial edema, and osteitis. CRS is divided into two phenotypes according to the presence or absence of nasal polyps: CRS with nasal polyp (CRSwNP) and CRS without nasal polyps (CRSsNP). Based on the underlying pathophysiologic mechanism, CRS is also classified as eosinophilic CRS and non-eosinophilic CRS, owing to Type 2 T helper (Th2)-based inflammation and Type 1 T helper (Th1)/Type 17 T helper (Th17) skewed immune response, respectively. Differences in tissue remodeling in CRS are suggested to be based on the clinical phenotype and endotypes; this is because fibrosis is prominent in CRSsNP, whereas edematous changes occur in CRSwNP, especially in the eosinophilic type. This review aims to summarize the latest information on the different mechanisms of airway remodeling in CRS according to distinct endotypes.
Immunologic and Non-Immunologic Mechanisms Leading to Airway Remodeling in Asthma
Cited by 10
| Viewed by 1626
Asthma increases worldwide without any definite reason and patient numbers double every 10 years. Drugs used for asthma therapy relax the muscles and reduce inflammation, but none of them inhibited airway wall remodeling in clinical studies. Airway wall remodeling can either be induced
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Asthma increases worldwide without any definite reason and patient numbers double every 10 years. Drugs used for asthma therapy relax the muscles and reduce inflammation, but none of them inhibited airway wall remodeling in clinical studies. Airway wall remodeling can either be induced through pro-inflammatory cytokines released by immune cells, or direct binding of IgE to smooth muscle cells, or non-immunological stimuli. Increasing evidence suggests that airway wall remodeling is initiated early in life by epigenetic events that lead to cell type specific pathologies, and modulate the interaction between epithelial and sub-epithelial cells. Animal models are only available for remodeling in allergic asthma, but none for non-allergic asthma. In human asthma, the mechanisms leading to airway wall remodeling are not well understood. In order to improve the understanding of this asthma pathology, the definition of “remodeling” needs to be better specified as it summarizes a wide range of tissue structural changes. Second, it needs to be assessed if specific remodeling patterns occur in specific asthma pheno- or endo-types. Third, the interaction of the immune cells with tissue forming cells needs to be assessed in both directions; e.g., do immune cells always stimulate tissue cells or are inflamed tissue cells calling immune cells to the rescue? This review aims to provide an overview on immunologic and non-immunologic mechanisms controlling airway wall remodeling in asthma.