Macrophage-derived CCL20 promotes abdominal aortic aneurysm progression via lymphocytes CCR6

Introduction: Abdominal aortic aneurysm (AAA) is a chronic vascular disease marked by chronic inflammation and immune dysregulation. The C-C motif chemokine ligand 20 (CCL20) - C-C motif chemokine receptor type 6 (CCR6) axis modulates immune responses in vascular diseases, but its role in AAA remains unclear. This study investigates the involvement of the CCL20-CCR6 axis in AAA formation. Methods: Single-cell RNA sequencing datasets and bulk RNA sequencing datasets were analyzed to assess cellular composition and transcriptional changes. Transcriptomic analysis, enzyme-linked immunosorbent assay, UK Biobank database analysis, CellChat analysis, immunofluorescence staining, and mouse models were employed to explore the CCL20-CCR6 axis in AAA. Results: Substantial immune cell infiltration (T lymphocytes & B lymphocytes) and loss of structural cells (fibroblasts, endothelial cells and smooth muscle cells) were identified using single-cell RNA sequencing datasets. Macrophage polarization was imbalanced, with enriched M1-like macrophages and elevated CCL20 secretion. Macrophages could promote the formation of AAA by recruiting a large number of immune cells via the CCL20-CCR6 axis. In vitro, CCL20 neutralization reduced immune cell recruitment; in vivo, the knockdown of this axis inhibited AAA progression. Conclusions: Macrophage-derived CCL20 aggravates lymphocyte recruitment via the CCR6, promoting AAA progression. CCL20 may serve as a biomarker for AAA. Targeting the CCL20-CCR6 axis could inhibit immune recruitment and AAA progression.