Roles of FOXP3 in experimental atherosclerosis of ApoE-knockout mice

WANG Zhi-xiao; MAO Xiao-bo; LIN Jin; WANG Cong-quan; ZHAN Zhong-qun; Li Da-zhu

摘要：Background Subtypes of T cells, called regulatory T cells (Treg cell), play a critical role in linuting autoimmune processes and inflammatory responses, The aim of this study was to explore functional roles of FOXP3 in the manifestation of atherosclerosis in Apolipoprotein E deficient (ApoE)-/- mice. Methods Lentivirus-mediated (siRNA) was used to knock down FOXP3 and FOXP3<'high+>CD4+ CD25+ T cells adoptive transfer assays in high fat diet ApoE-/- mice were done. The resulting atherosclerotic lesions were assessed by determining FOXP3 transcript levels and investigating the expression of FOXP3 protein in different tissues.Results Animals treated with siRNA of FOXP3 showed a significant increase in atherosclerotic lesion formation and a reduction in the number of FOXP3+CD4+CD25+ T cells compared with other groups. Transfer of FOXP3<'high+>CD4+CD25+ T cells significantly decreased atherosclerotic plaque formation and increased the number of FOXP3+CD4+ CD25+ T cells. FOXP3 protein levels and FOXP3 transcript levels were lowest in the siRNA group, and were highest in tissues from the Treg transfer group. Conclusion FOXP3 plays an important role in regulating the inflammatory response within the atherosclerotic lesion. It can inhibit significantly the progression of the atherosclerosis plaque in ApoE /- mice.