<p>How Do Innate Immune Cells Contribute to Airway Remodeling in COPD Progression?</p>

Abstract

Recently, the therapeutic potential of immune-modulation during the progression of chronic obstructive pulmonary disease (COPD) has been attracting increasing interest. However, chronic inflammatory response has been oversimplified in descriptions of the mechanism of COPD progression. As a form of first-line airway defense, epithelial cells exhibit phenotypic alteration, and participate in epithelial layer disorganization, mucus hypersecretion, and extracellular matrix deposition. Dendritic cells (DCs) exhibit attenuated antigen-presenting capacity in patients with advanced COPD. Immature DCs migrate into small airways, where they promote a pro-inflammatory microenvironment and bacterial colonization. In response to damageassociated molecular patterns (DAMPs) in lung tissue affected by COPD, neutrophils are excessively recruited and activated, where they promote a proteolytic microenvironment and fibrotic repair in small airways. Macrophages exhibit decreased phagocytosis in the large airways, while they demonstrate high pro-inflammatory potential in the small airways, and mediate alveolar destruction and chronic airway inflammation. Natural killer T (NKT) cells, eosinophils, and mast cells also play supplementary roles in COPD progression; however, their cellular activities are not yet entirely clear. Overall, during COPD progression, "exhausted" innate immune responses can be observed in the large airways. On the other hand, the innate immune response is enhanced in the small airways. Approaches that inhibit the inflammatory cascade, chemotaxis, or the activation of inflammatory cells could possibly delay the progression of airway remodeling in COPD, and may thus have potential clinical significance.

Single-cell transcriptomics reveal cell type-specific molecular changes and altered intercellular communications in chronic obstructive pulmonary disease

“…The copyright holder for this this version posted February 25, 2021. ; https://doi.org/10.1101/2021.02.23.432590 doi: bioRxiv preprint equally important (44)(45)(46) Meanwhile, AT2s in COPD lungs showed not only the inhibited differentiation to AT1s, but also increased expression of several positive apoptotic regulators in its COPD-associated DEGs, such as HES1 (30) and KLF4 (31). Thus, AT2s were the potential killing target of hMono3s.…”

“…In the past, adaptive immune system has been extensively studied in investigations of COPD pathogenesis due to the conventional view that the adaptive immune response is crucial for the type of long-term inflammation that is required to drive chronic respiratory disease such as COPD. Although mounting evidences are emerging that the participation of innate immune system in chronic respiratory disease are at least equally important (44–46), monocytes have long been unappreciated mainly due to its plasticity to both DCs and macrophages. Moreover, the heterogeneity of this cellular population further increased the difficulty of research.…”

Unraveling the Interconnection Patterns Across Lung Microbiome, Respiratory Diseases, and COVID-19

“…At the same time, in the small airways macrophages demonstrate high pro-inflammatory potential ( Shapiro, 1999 ; Bu et al., 2020 ) ( Figure 1 ). Moreover, Natural killer T (NKT) cells, eosinophils, and mast cells are incriminated to have a complementary function in the inflammatory process of small and mediate alveolar tissue that leads to chronic airway inflammation ( O’byrne and Postma, 1999 ).…”

“…Neutrophils’ recruitment and activation are observed in response to inflammation status. However, macrophages exhibit decreased phagocytosis in the large lung airways during the progression of chronic obstructive pulmonary disease (COPD) ( Bu et al., 2020 ). Dropping of the phagocytic capacity of macrophages impair the lung function and produce a chronic inflammation status ( Bu et al., 2020 ).…”

Evaluation of Naringenin as a Promising Treatment Option for COPD Based on Literature Review and Network Pharmacology

“…Airway remodeling is a direct cause of airflow limitation in COPD patients with hyperplasia of the airway epithelial cells, thickening of the reticular basement membrane, airway smooth muscle proliferation, deposition of collagen, and airway fibrosis [72]. The currently available therapies for airway remodeling in COPD are mainly bronchodilators and glucocorticosteroids, but patients are poorly controlled by them [73]. Although the reversibility of airway remodeling was observed in animal models, there is no available therapy proven to reverse airway remodeling in patients with COPD or asthma [74,75].…”