Study on the Role and Mechanism of γδ T Cells in Atherosclerosis Under a High-Fat Diet

This study aimed to investigate the effects of γδ T cell inhibition under a high-fat diet (HFD) on metabolic function, immune inflammation, gut microbiota, and atherosclerosis (AS) progression in ApoE ^-/- mice.

ApoE ^-/- mice were assigned to three groups: a control group (normal diet), a model group (HFD), and an intervention group (HFD + γδ T cell receptor (TCR) monoclonal antibody). After 12 weeks, flow cytometry was used to assess γδ T cell levels, and cytokines (interferon-gamma (IFN-γ), IL-17A) were measured. Inflammatory markers in blood and adipose tissue were quantified, gut microbiota composition was analyzed via fecal metagenomics, and atherosclerosis was evaluated using Oil Red O, Masson's trichrome, and hematoxylin and eosin (HE) staining methods.

The HFD activated γδ T cells and increased pro-inflammatory cytokines in ApoE ^-/- mice. Treatment with the γδ TCR monoclonal antibody suppressed γδ T cells, reduced IFN-γ and IL-17A expression, improved lipid profiles, and decreased tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6 levels. Gut microbiota analysis showed an increase in beneficial bacteria, and histological staining (Oil Red O, HE, and Masson's trichrome) confirmed a reduction in atherosclerotic lesion burden.

The γδ T cells contribute to AS development under the HFD. Inhibition of γδ T cells reduces inflammation, improves gut microbiota composition, and attenuates atherosclerosis progression.