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

Single-cell RNA sequencing analysis of AAA datasets revealed substantial immune cell infiltration and loss of structural cells.

• T lymphocytes and B lymphocytes were enriched in AAA tissue compared to normal aortic tissue.
• Structural cells including fibroblasts, endothelial cells, and smooth muscle cells were depleted in AAA.
• Single-cell RNA sequencing datasets were analyzed to assess cellular composition and transcriptional changes in AAA.

Macrophage polarization was imbalanced in AAA, with enriched M1-like macrophages and elevated CCL20 secretion.

• M1-like macrophages were found to be enriched relative to M2-like macrophages in AAA tissue.
• CCL20 secretion was elevated in association with M1-like macrophage polarization.
• CellChat analysis was employed to explore intercellular communication involving the CCL20-CCR6 axis.

Macrophages promote AAA formation by recruiting immune cells via the CCL20-CCR6 axis.

• CellChat analysis identified macrophage-to-lymphocyte signaling through the CCL20-CCR6 axis as a key communication pathway.
• Immunofluorescence staining confirmed co-localization patterns consistent with CCL20-CCR6 mediated recruitment.
• Transcriptomic analysis supported upregulation of CCL20-CCR6 axis components in AAA tissue.

In vitro CCL20 neutralization reduced immune cell recruitment.

• Neutralization of CCL20 in cell culture experiments led to reduced recruitment of lymphocytes.
• These in vitro experiments provided mechanistic support for the role of CCL20 in driving immune cell migration.

In vivo knockdown of the CCL20-CCR6 axis inhibited AAA progression in mouse models.

• Mouse models of AAA were used to evaluate the functional role of the CCL20-CCR6 axis in vivo.
• Knockdown of this axis resulted in inhibited AAA progression compared to control animals.
• These findings were corroborated by UK Biobank database analysis supporting CCL20's association with AAA in human populations.

CCL20 was identified as a potential biomarker for AAA.

• Enzyme-linked immunosorbent assay (ELISA) was used to measure CCL20 levels in relation to AAA.
• UK Biobank database analysis was performed to support the association between CCL20 and AAA at a population level.
• Bulk RNA sequencing datasets were analyzed to confirm transcriptional upregulation of CCL20 in AAA.