Exploring Immune Dysfunction in Bronchiectasis: A Focus on Natural Killer Cells using Single-Cell Transcriptomes

Abstract Bronchiectasis describes chronic airway inflammation involving various immune cells; however, little information is available regarding cell-type-specific pathogenic changes that influence disease development of bronchiectasis. We aimed to investigate immune dysregulation in bronchiectasis through single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs). PBMCs from eight bronchiectasis patients and eight healthy controls were isolated and subjected to scRNA-seq using the 10X Genomics platform. Frequencies of immune cell subsets were compared between groups, and functional implications were inferred based on transcriptional signatures. The overall innate immune cell composition was similar between bronchiectasis patients and healthy controls, but significant subset-level alterations were observed. Bronchiectasis patients exhibited increased CD4 + and CD8 + effector memory T cells, suggesting chronic inflammatory activated status of T cells. Notably, FCER1G + NK cells were significantly reduced in bronchiectasis patients, accompanied by decreased expression of chemokines such as CCL3, CCL4, XCL1, and XCL2. In bronchiectasis patients, pro-inflammatory CD14 + monocytes tended to be decreased, showing reduced CXCR4 expression. Our findings reveal distinct immune alterations in bronchiectasis, especially involving NK cells and monocytes. The depletion of FCER1G + NK cells and downregulation of CXCR4 in monocytes suggest a disrupted innate immune cascade that may contribute to disease progression in bronchiectasis.