Dysregulated Functions of Lung Macrophage Populations in COPD

Figure 3

Future directions in COPD lung macrophage population research. Recent advances in Immunogenetics and Structural Biology make it possible to evaluate the heterogeneity of lung macrophage populations. In particular, single cell RNA sequencing can identify homogeneous macrophage subsets with distinct transcriptomes and functions. Mass cytometry can complement and validate initial findings establishing prognosis/diagnosis biomarkers for human patients with COPD. Moreover, analysis of the nuclear heterochromatin state with ATAC sequencing and subsequent validation with ChIP-sequencing can shed light on the epigenetic regulation of lung macrophage populations and highlight the molecular mechanisms responsible for their functions in vivo. Lastly, the role of AMs, IMs, and lung monocytes warrants further investigation in order to better understand the contributions of each macrophage population to COPD progression and severity. Transcriptome analysis will determine whether these populations are distinct or part of a differentiation continuum from the monocyte to the AM phenotype and will associate gene expression with unique biological processes.