The Th17/Treg functional imbalance during atherogenesis in ApoE(-/-) mice

Objective: Atherosclerosis is a chronic inflammatory disease regulated by T lymphocyte subsets. Recently, CD4 + CD25 + Foxp3 + regulatory T (Treg) cells and Th17 cells have been described as two distinct subsets and have the opposite effects on autoimmunity. Clinical observation has revealed that the Th17/Treg imbalance exists in patients with acute coronary syndrome. We investigated whether the Th17/Treg functional imbalance existed during atherogenesis in ApoE −/− mice. Methods and results: Th17/Treg functions at different levels including cell frequencies, related cytokine secretion and key transcription factors were investigated comparatively between ApoE −/− mice and their age-matched C57BL/6J mice. The results demonstrated that ApoE −/− mice revealed significantly increased secretion of Th17 related cytokines (IL-17 and IL-6) and expression of transcription factor (RORγt) levels and obviously decreased number in Treg cells, secretion of Treg related cytokines (TGF-β 1 ) and expression of transcription factor (Foxp3) levels as compared with age-matched C57BL/6J mice. Th17 related mediators reached their maximum expression values at the early stage (8–16 weeks of age) in ApoE −/− mice, and then followed by continuous depression of their expression levels. Meanwhile, the expression of Treg related mediators was much lower in ApoE −/− mice than in their age-matched wild-type littermates. Conclusions: Th17/Treg functional imbalance exists during atherogenesis in ApoE −/− mice, suggesting a potential role of Th17/Treg imbalance in the formation and progression of atherosclerosis.