Background
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by inflammation and airway remodeling. Lymphoid follicles play a crucial role in acquired immunity and the development of COPD. However, the precise mechanisms of lymphoid follicle formation in COPD and the effects of cigarette smoke (CS) exposure on this process remain unclear. Epithelial-mesenchymal transition (EMT) is implicated in the progression of COPD and may serves as a source of stromal cells that produce chemokines crucial for lymphoid follicle formation. This study aims to clarify the contributions and mechanisms of EMT in lymphoid follicle genesis in COPD, focusing specifically on the role of CXCL13.
Conclusion
Lymphoid follicles are associated with enhanced EMT in COPD. EMT may act as a key driver of the adaptive immune response in COPD by promoting a microenvironment conducive to lymphoid follicles formation through the production of CXCL13. This study provides valuable insights into the mechanisms underlying lymphoid follicle formation in COPD and identifies potential therapeutic targets.
Methods
Lung tissue samples were obtained from patients with COPD, smokers, and non-smokers. Immunohistochemistry was performed to assess the lymphoid follicles, EMT-related markers, and CXCL13 expression. In vitro experiments were conducted using CS extract (CSE)-stimulated immortalized human bronchial epithelial cells (iHBECs) to induce EMT. The expression of EMT-related markers and CXCL13 in CSE-stimulated iHBECs was analyzed using Western blotting, real-time PCR, and immunofluorescence staining. The effect of an EMT inhibitor on CXCL13 expression was also examined.
Results
Patients with COPD and lymphoid follicles exhibited significantly lower forced expiratory volume in 1 s (% predicted) values than those without lymphoid follicles. Enhanced EMT changes were observed in patients with COPD and lymphoid follicles. Increased EMT-related markers and CXCL13 expression were observed in CSE-stimulated iHBECs, and CXCL13 expression gradually increased over time. Inhibiting EMT downregulated CXCL13 expression in iHBECs.