CCL18 aggravates atherosclerosis by inducing CCR6-dependent T-cell influx and polarization

Area of Science:

• Immunology
• Cardiovascular Biology
• Inflammation Research

Background:

• CC chemokine ligand 18 (CCL18) is elevated in chronic inflammation and acute cardiovascular syndromes.
• CCL18 is highly expressed in human atherosclerotic plaques, particularly in macrophages.

Purpose of the Study:

• To investigate the role of CCL18 in the pathogenesis of atherosclerosis.
• To identify the receptor mediating CCL18's effects in immune cells.

Main Methods:

• CCL18 administration in ApoE-/- and PCSK9mut mice on Western diets.
• In vitro studies using human and mouse T cells, including CCR6-deficient cells.
• In vivo inflammation model using wild-type and CCR6-deficient mice.

Main Results:

• CCL18 administration increased plaque burden and CD3+ T cell infiltration in mice.
• CCR6 was identified as the functional receptor for CCL18, mediating chemotaxis and signaling.
• CCL18 induced T cell-mediated inflammation in vivo, dependent on CCR6.

Conclusions:

• The CCL18/CCR6 axis is a novel regulator of immune responses in atherosclerosis.
• Targeting the CCL18/CCR6 pathway may offer therapeutic strategies for cardiovascular disease.