Division of Biopharmaceutics, Leiden University, Leiden, The Netherlands.
Atherosclerosis. 2010 Mar;209(1):74-80. doi: 10.1016/j.atherosclerosis.2009.08.041. Epub 2009 Aug 31.
Regulatory T cells are crucial for immune homeostasis and an impaired regulatory T cell function results in many pathological conditions. Regulatory T cells have already been described to be protective in atherosclerosis. However the exact contribution of Foxp3-expressing natural regulatory T cells in atherosclerosis has not been elucidated yet.
In this study we vaccinated LDL receptor deficient mice with dendritic cells which are transfected with Foxp3 encoding mRNA and studied the effect on initial atherosclerosis. Vaccination against Foxp3 resulted in a reduction of Foxp3(+) regulatory T cells in several organs and in an increase in initial atherosclerotic lesion formation. Furthermore we observed an increase in plaque cellularity and increased T cell proliferation in the Foxp3 vaccinated mice.
We further establish the protective role of Tregs in atherosclerosis. The results illustrate the important role for Foxp3-expressing regulatory T cells in atherosclerosis, thereby providing a potential opportunity for therapeutic intervention against this disease.
调节性 T 细胞对于免疫稳态至关重要,而调节性 T 细胞功能受损会导致许多病理状况。调节性 T 细胞已被证明在动脉粥样硬化中具有保护作用。然而,Foxp3 表达的天然调节性 T 细胞在动脉粥样硬化中的确切作用尚未阐明。
在这项研究中,我们用转染 Foxp3 编码 mRNA 的树突状细胞对 LDL 受体缺陷小鼠进行了疫苗接种,并研究了其对早期动脉粥样硬化的影响。针对 Foxp3 的疫苗接种导致多个器官中 Foxp3(+)调节性 T 细胞减少,并导致初始动脉粥样硬化病变形成增加。此外,我们观察到 Foxp3 接种小鼠的斑块细胞增多和 T 细胞增殖增加。
我们进一步证实了 Treg 在动脉粥样硬化中的保护作用。这些结果说明了 Foxp3 表达的调节性 T 细胞在动脉粥样硬化中的重要作用,从而为针对这种疾病的治疗干预提供了潜在机会。