Characterization of IL-6R-expressing monocytes in the lung of patients with chronic obstructive pulmonary disease

Background: Monocytes play a crucial role in innate immune responses for host defense, however, their involvement in chronic obstructive pulmonary disease (COPD) remains poorly understood. We previously identified a subset of monocytes in COPD lung tissues characterized by high interleukin-6 receptor (IL-6R) expression. This study aimed to characterize the phenotypes of IL-6R^hi monocytes in the lungs of COPD patients. Methods: Using flow cytometry, we assessed the abundance of pulmonary CD14⁺IL-6R^hi cells in never smokers (CNS), control ex-smokers (CES) and COPD patients. IL-6 expression in CD14⁺ monocytes isolated from the peripheral blood of patients with COPD was also examined. CD45⁺CD206^–CD14⁺IL-6R^hi and CD45⁺CD206^–CD14⁺IL-6R^–/lo cells were isolated from COPD lung tissues for transcriptome analysis. A monocyte line THP1 cell with constitutive IL-6R expression was stimulated with recombinant IL-6, followed by RNA sequencing to evaluate the IL-6 responsiveness of IL-6R⁺ monocytes. Results: The number of pulmonary CD14⁺IL-6R^hi monocytes was elevated in COPD patients compared to CNS, whereas CD14⁺ monocytes in the peripheral blood of COPD patients did not express IL-6R. Upregulated mRNA expression in CD14⁺IL-6R^hi monocytes was associated with chemotaxis, monocyte differentiation, fatty acid metabolism and integrin-mediated signaling pathway. Stimulation of THP1 cells with recombinant IL-6 induced changes in the expression of genes linked to chemotaxis and organism development. Conclusion: In patients with COPD, CD14⁺IL-6R^hi monocytes are increased in lung tissues compared to those in CNS. They exhibit a transcriptome profile different from that of CD14⁺IL-6R^–/lo monocytes.