Immunologic and Non-Immunologic Mechanisms Leading to Airway Remodeling in Asthma

Abstract

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.

Innate Lymphoid Cells Are Required to Induce Airway Hyperreactivity in a Murine Neutrophilic Asthma Model

“…This is however in line with features observed in non-allergic asthma patients ( 46 – 48 ). Several studies have shown that non-allergic asthma patients have less epithelial damage, less smooth muscle thickening, or other structural changes compared to allergic asthmatic patients ( 46 – 49 ). This suggests that this model resembles some and not all classical features of asthma, but previous studies in human asthma learned that not all these features are to be found in all asthma phenotypes.…”

Persistent Airway Hyperresponsiveness Following Recovery from Infection with Pneumonia Virus of Mice

“…AHR is defined as intermittent and reversible airway narrowing and is manifested clinically as wheezing; shortness of breath; and in severe cases, hypoxia and death [ 36 ]. AHR results from both increased contraction of airway smooth muscle (ASM) in response to inflammatory mediators and airway remodeling resulting from inflammation [ 37 ]. In humans, AHR is diagnosed by the use of spirometry, which is a procedure that facilitates the estimation of airway resistance via measurements of the air volumes expelled during forced expiration at baseline and after challenge with bronchoconstrictors and/or bronchodilators [ 38 ].…”

Mojabanchromanol Isolated from Sargassum horneri Attenuates Particulate Matter Induced Inflammatory Responses via Suppressing TLR2/4/7-MAPK Signaling in MLE-12 Cells

“…Activated MAPK pathway, upon PM exposure, was identified to mediate the secretion of pro-inflammatory cytokines IL-1β, IL-6, and IL-33 in alveolar epithelial cells [ 33 , 34 , 35 ]. PM-induced IL-6 is essential for initiating inflammation, coagulation, and fibrin deposition in lung [ 36 , 37 ].…”