CD80+ Macrophage-Induced IL-17+CD8+ T cells accumulate in hyperlipidemic patients and murine vascular lesions to promote atherosclerotic progression

Tc17 cells (IL-17 + CD8+T) are found in many inflammatory diseases. However, the distribution, regulation, and function of Tc17 cells in ApoE deficient-induced atherosclerosis are currently largely unexplored. The percentage of Tc17 cells, monocytes and IL-1β+ monocytes in blood of hyperlipidemic patients or healthy donors were analyzed by flow cytometry. The content of IL-1β in plasma was detected by ELISA. Correlations between parameters of clinical samples were assessed using Spearman r correlation analysis or linear regression analysis as appropriate. Aorta, blood, spleen, and bone marrow of atherosclerotic mice with different stages were collected for flow cytometry to analyze the percentage of Tc17 cells and monocytes/macrophages. Hearts were collected for Oil Red O staining, Masson’s staining, immunofluorescence staining or immunohistochemistry staining. GEO database (GSE43292) was used to analyze the expression of Tc17 cell-related inducers in plaques of AS patients. CD8+T cells and macrophages were isolated for ex vivo function assays. Adoptive transfer and IL-1β neutralization experiments were utilized for in vivo mechanism assays. Higher populations of Tc17 cells, IL-1β+monocytes or CD80+ monocytes were found in the peripheral blood of hyperlipidemic patients compared to that in healthy donors. In addition, positive correlation between Tc17 cells and CD80+ monocytes was observed in hyperlipidemic patients. Furthermore, Tc17 cells and CD80+ monocytes/macrophages increased in the aorta, blood, spleen, and bone marrow of atherosclerotic mice, reaching the highest level on week 12 post feeding. Based on the analysis of GSE43292, we found increased IL-1β expression in AS plaques, not the other inducing differentiation factors of Tc17 cells, compared to normal tissues. Finally, ex vivo co-culture and transwell experiment and in vivo adoptive transfer and IL-1β neutralization experiments confirmed that CD80+ macrophages promoted Tc17 cells expansion by IL-1β in vascular lesions and facilitated murine atherosclerotic progression. The present results show that suppressing IL-1β expression by preventing CD80+ macrophage polarization may alleviate atherosclerosis through the reduction of Tc17 cells in atherosclerotic lesions. Our study demonstrates that decreasing Tc17 cells population by the inhibition of CD80+ macrophage-derived IL-1β is a potentially promising therapeutic strategy for the treatment of atherosclerosis.