Homeostatic cross-talk between host inflammation and the barrier framework is essential to maintaining barrier integrity at mucosal surfaces in the lung. However, a dysregulated or overly amplified host response often results in damage-associated structural changes to the barrier, leading to altered epithelial and/or endothelial cell phenotypes during acute or chronic inflammatory conditions. For instance, influenza infection recruits CCR2hi inflammatory monocytes (IMs), which interact with alveolar epithelial cells in the lung. The cross-talk involves the physical interactions between IMs and alveolar epithelia, as well as the inflammatory cytokine-mediated induction of epithelial response in the lungs. These immune events promote the dysregulation of epithelial tight junction (TJs) proteins, cilia function, mucus production, and cell differentiation, leading to an increased susceptibility to bacterial diseases in influenza-infected hosts. Due to enormous antigenic variation in the influenza virus, the host memory T cell response is of limited significance, and the role of monocyte-mediated epithelial damage serves a key element of therapeutic intervention.
A dominant Th2 phenotype characterizes the chronic lung inflammation arising from allergic asthma. Epithelial IL-33 response promotes the recruitment of allergen-specific Th2 cells producing signature cytokines, IL-4, IL-5, and IL-13. Additionally, an emerging role of innate lymphoid cells 2 (ILC2S) and Th9 cells has been noted in asthma pathophysiology. Th2 cytokines play a crucial role in the recruiting of eosinophils to the airway. In asthma, acute inflammatory-epithelial cross-talk manifests at two levels: (1) IL-4, IL-5 and IL-13 cytokine-mediated induction of epithelial response, and (2) eosinophil-epithelial cross-talk. These immune interactions result in epithelial changes such as dysregulation of TJs, epithelial leaking, goblet hyperplasia, and sub-epithelial fibrosis. Clinically, there exists significant overlap in asthma and COPD phenotypes. Smoke-related changes in lung physiology can exacerbate asthma pathology or vice-versa.
A significant knowledge gap exists in our understanding of key signaling pathways in lung alveolar epithelia involved in the loss of barrier integrity during acute and chronic inflammatory conditions. A better understanding of these interactions will lead to the development of novel therapies that are better able to combat changes associated with causing dysregulation of barrier integrity at lung mucosal surfaces.
Therefore, the goal of this Research Topic is to outline the most notable and current understandings of the cross-talk between immune cells involved in acute and chronic inflammation with that of barrier framework in the lung, leading to the susceptibility for infections and the development of the chronic inflammatory disorders.
We welcome the submission of Review, Mini-Review and Original Research articles covering, but not limited to, the following topics:
1. The consequences of acute and chronic inflammation for the susceptibility of bacterial and viral infections in the lung.
2. The consequence of the cross-talk between immune cells involved in acute/chronic inflammation and the barrier framework on lung pathology.
3. The damage-response framework in the lung: how to better define the endpoints of beneficial and pathological inflammation in pulmonary infection and inflammatory diseases.
Homeostatic cross-talk between host inflammation and the barrier framework is essential to maintaining barrier integrity at mucosal surfaces in the lung. However, a dysregulated or overly amplified host response often results in damage-associated structural changes to the barrier, leading to altered epithelial and/or endothelial cell phenotypes during acute or chronic inflammatory conditions. For instance, influenza infection recruits CCR2hi inflammatory monocytes (IMs), which interact with alveolar epithelial cells in the lung. The cross-talk involves the physical interactions between IMs and alveolar epithelia, as well as the inflammatory cytokine-mediated induction of epithelial response in the lungs. These immune events promote the dysregulation of epithelial tight junction (TJs) proteins, cilia function, mucus production, and cell differentiation, leading to an increased susceptibility to bacterial diseases in influenza-infected hosts. Due to enormous antigenic variation in the influenza virus, the host memory T cell response is of limited significance, and the role of monocyte-mediated epithelial damage serves a key element of therapeutic intervention.
A dominant Th2 phenotype characterizes the chronic lung inflammation arising from allergic asthma. Epithelial IL-33 response promotes the recruitment of allergen-specific Th2 cells producing signature cytokines, IL-4, IL-5, and IL-13. Additionally, an emerging role of innate lymphoid cells 2 (ILC2S) and Th9 cells has been noted in asthma pathophysiology. Th2 cytokines play a crucial role in the recruiting of eosinophils to the airway. In asthma, acute inflammatory-epithelial cross-talk manifests at two levels: (1) IL-4, IL-5 and IL-13 cytokine-mediated induction of epithelial response, and (2) eosinophil-epithelial cross-talk. These immune interactions result in epithelial changes such as dysregulation of TJs, epithelial leaking, goblet hyperplasia, and sub-epithelial fibrosis. Clinically, there exists significant overlap in asthma and COPD phenotypes. Smoke-related changes in lung physiology can exacerbate asthma pathology or vice-versa.
A significant knowledge gap exists in our understanding of key signaling pathways in lung alveolar epithelia involved in the loss of barrier integrity during acute and chronic inflammatory conditions. A better understanding of these interactions will lead to the development of novel therapies that are better able to combat changes associated with causing dysregulation of barrier integrity at lung mucosal surfaces.
Therefore, the goal of this Research Topic is to outline the most notable and current understandings of the cross-talk between immune cells involved in acute and chronic inflammation with that of barrier framework in the lung, leading to the susceptibility for infections and the development of the chronic inflammatory disorders.
We welcome the submission of Review, Mini-Review and Original Research articles covering, but not limited to, the following topics:
1. The consequences of acute and chronic inflammation for the susceptibility of bacterial and viral infections in the lung.
2. The consequence of the cross-talk between immune cells involved in acute/chronic inflammation and the barrier framework on lung pathology.
3. The damage-response framework in the lung: how to better define the endpoints of beneficial and pathological inflammation in pulmonary infection and inflammatory diseases.