Highway to heal: Influence of altered extracellular matrix on infiltrating immune cells during acute and chronic lung diseases

Abstract

Environmental insults including respiratory infections, in combination with genetic predisposition, may lead to lung diseases such as chronic obstructive pulmonary disease, lung fibrosis, asthma, and acute respiratory distress syndrome. Common characteristics of these diseases are infiltration and activation of inflammatory cells and abnormal extracellular matrix (ECM) turnover, leading to tissue damage and impairments in lung function. The ECM provides three-dimensional (3D) architectural support to the lung and crucial biochemical and biophysical cues to the cells, directing cellular processes. As immune cells travel to reach any site of injury, they encounter the composition and various mechanical features of the ECM. Emerging evidence demonstrates the crucial role played by the local environment in recruiting immune cells and their function in lung diseases. Moreover, recent developments in the field have elucidated considerable differences in responses of immune cells in two-dimensional versus 3D modeling systems. Examining the effect of individual parameters of the ECM to study their effect independently and collectively in a 3D microenvironment will help in better understanding disease pathobiology. In this article, we discuss the importance of investigating cellular migration and recent advances in this field. Moreover, we summarize changes in the ECM in lung diseases and the potential impacts on infiltrating immune cell migration in these diseases. There has been compelling progress in this field that encourages further developments, such as advanced in vitro 3D modeling using native ECM-based models, patient-derived materials, and bioprinting. We conclude with an overview of these state-of-the-art methodologies, followed by a discussion on developing novel and innovative models and the practical challenges envisaged in implementing and utilizing these systems.

Anoikis resistance of small airway epithelium is involved in the progression of chronic obstructive pulmonary disease

“…Previous research has demonstrated that the infiltration and activation of inflammatory cells lead to tissue damage and impairments in lung function ( 50 ). Meanwhile, functional annotations revealed that DEGs between Cluster1 and Cluster2 were predominantly enriched for terms associated with immune response, suggesting that anoikis might be involved in the immune regulation in COPD.…”

Neo-epitope detection identifies extracellular matrix turnover in systemic inflammation and sepsis

“…Not only can in ammation lead to aberrant ECM turnover, in turn causing tissue remodelling, this aberrant remodelling itself could contribute to a pro-in ammatory tissue environment. This is mediated through ECM fragments and matricellular proteins capable of facilitating immune cell migration, activation, and persistent in ammation, thereby impairing organ recovery [47] and creating a vicious circle detrimental to the patient.…”

Potential marker genes for chronic obstructive pulmonary disease revealed based on single-cell sequencing and Mendelian randomization analysis

“…The immunological profile of COPD during its progression remains unclear, so further studies of immune cell infiltration in COPD are still needed. The immune inflammation associated with COPD is at the heart of the disease, which is one of the reasons why current treatments have failed to stop the progression of the disease and the continued damage to lung tissue [ 29 ]. Previous studies have shown that the effector molecule functions of neutrophils and macrophages involved in chronic inflammation in COPD are suppressed [ 30 , 31 ].…”