Macrophages Orchestrate Airway Inflammation, Remodeling, and Resolution in Asthma

Abstract

Asthma is a heterogenous chronic inflammatory lung disease with endotypes that manifest different immune system profiles, severity, and responses to current therapies. Regardless of endotype, asthma features increased immune cell infiltration, inflammatory cytokine release, and airway remodeling. Lung macrophages are also heterogenous in that there are separate subsets and, depending on the environment, different effector functions. Lung macrophages are important in recruitment of immune cells such as eosinophils, neutrophils, and monocytes that enhance allergic inflammation and initiate T helper cell responses. Persistent lung remodeling including mucus hypersecretion, increased airway smooth muscle mass, and airway fibrosis contributes to progressive lung function decline that is insensitive to current asthma treatments. Macrophages secrete inflammatory mediators that induce airway inflammation and remodeling. Additionally, lung macrophages are instrumental in protecting against pathogens and play a critical role in resolution of inflammation and return to homeostasis. This review summarizes current literature detailing the roles and existing knowledge gaps for macrophages as key inflammatory orchestrators in asthma pathogenesis. We also raise the idea that modulating inflammatory responses in lung macrophages is important for alleviating asthma.

Research trends on airway remodeling: A bibliometrics analysis

“…Airway remodeling refers to the structural and functional changes of airway tissue caused by repeated chronic inflammatory stimulation injury and an incomplete repair, which is more common in chronic airway inflammatory diseases such as asthma and COPD [ 33 ]. It is a significant cause of irreversible airway stenosis and airflow limitation.…”

“…Airway remodeling is present in many obstructive pulmonary diseases, and previous studies suggest that airway remodeling is an event triggered by chronic airway inflammation, but recent studies suggest that airway remodeling may emerge as an initial event, even before triggering any respiratory symptoms and inflammation process [ 1 , 45 ]. Therefore, there are still many mysteries about airway remodeling in obstructive pulmonary disease, and there is currently a lack of effective interventions for airway remodeling in clinical practice, which is one of the most challenging problems in treating respiratory diseases and is the goal of future treatment [ 33 ]. (2) Noninvasively Assessing: Computed tomography (CT) and magnetic resonance imaging (MRI) techniques can accurately assess the three-dimensional lung structure of patients.…”

Unveiling the Causal Association Between Noninfectious Respiratory Disorders and Sepsis Through Mendelian Randomization Analysis

“…Activated immune cells may have protective effects against infections 5,41 . Furthermore, scholarly evidence suggests that unique immunoregulatory pathways may be involved in mitigating the systemic spread of inflammatory reactions in individuals with asthma, potentially reducing the severity of sepsis 42,43 . The prevalence of Th2-type immune responses may also aid in dampening the hyperinflammatory reactions associated with sepsis 44 .…”

Comprehensive analysis of lung macrophages and dendritic cells in two murine models of allergic airway inflammation reveals model- and subset-specific accumulation and phenotypic alterations

“…In mice and humans, tissue resident macrophages are myeloid sentinel cells located in all organs. Resident macrophages in mucosal tissues have received increasing attention and numerous studies have demonstrated that these cells play critical roles in maintaining and restoring tissue immune homeostasis ( 6 , 7 ). It is well established that the lung harbors two distinct populations of macrophages: alveolar macrophages (AMs) and interstitial macrophages (IMs), with IMs dividing in several subsets ( 8 ).…”