The significance of CD16+ monocytes in the occurrence and development of Chronic Thromboembolic Pulmonary Hypertension: insights from single-cell RNA sequencing

Our current understanding of the pathobiology of chronic thromboembolic pulmonary hypertension (CTEPH) is primarily based on studies using specimens obtained through pulmonary endarterectomy (PEA). However, there is a significant gap in our knowledge regarding the characteristics and functions of circulating immune cells in CTEPH patients. To address this gap, our study aims to characterize the peripheral blood circulating immune cells in CTEPH patients, with a particular focus on monocytes. In this study, we performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) extracted from five CTEPH patients. This approach allowed us to identify various immune cell types present in the peripheral blood, including monocytes, T cells, and B cells. Notably, we observed an increased proportion of CD16+ monocytes in CTEPH patients. This monocyte subset exhibited distinct transcriptional profiles, indicating their involvement in critical biological processes such as cell adhesion, T cell activation, coagulation, and platelet activation. Our findings suggest that CD16+ monocytes may play a significant role in the pathogenesis of CTEPH, particularly in pulmonary arterial thrombosis and intimal remodeling. Furthermore, we observed that this subset of monocytes might be recruited into the pulmonary artery intima and differentiate into macrophages characterized by high IL-1ß expression, potentially contributing to disease progression. This study provides new insights into the immune landscape of CTEPH and highlights the potential role of CD16+ monocytes in the disease's pathophysiology. Overall design: The study focuses on the characterization of circulating immune cells in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We utilized single-cell RNA sequencing (scRNA-seq) to analyze peripheral blood mononuclear cells (PBMCs) from five CTEPH patients. The primary aim was to identify and profile various immune cell types, with a specific focus on the monocyte population.