动脉粥样硬化(Atherosclerosis, AS)是多种心脑血管疾病的主要病理基础。申请者和他人的研究均已证明，CCR6/Mip-3α轴通过调控CCR6+ 细胞炎症部位的迁移及释放IL-17等炎症因子，参与多种慢性炎症性疾病的病理生理机制。AS也是一种慢性炎症性病变，但CCR6/Mip-3α轴是否参与AS发病未见报道。我们的预初研究发现：在AS患者的动脉壁存在大量CCR6+ T 细胞以及表达Mip-3α的巨噬细胞聚集。由此我们提出如下假设：CCR6/Mip-3α轴可能参与AS发病机制，阻断该轴对AS的形成将起抑制作用。为此，我们采用已经构建成的CCR6-/-apoE-/- 双基因缺陷和apoE-/- 小鼠模型，探索CCR6/Mip-3α轴在AS发病中的作用及分子机制。本课题"CCR6/Mip-3α轴"的AS发病假说如被证实，将为AS发病的炎症学说提出又一新的分子机制和潜在药物治疗靶点。

Atherosclerosis (AS) is the major pathological basis for a variety of cardiovascular diseases. In agreement with others, we have found that CCR6/Mip-3α axis plays a critical role in the development of chronic inflammatory disorders, and the axis is involved in a variety of pathophysiological mechanisms of chronic inflammation through regulating CCR6+ T- cell migration and releasing IL-17 and other inflammatory factors. AS is a chronic inflammatory disease in which the role CCR6/Mip-3α axis remains unclear. Our preliminary data showed that not only CCR6+ T-cells but also macrophage expressing Mip-3α infiltrated the arterial wall of AS patients. Thus, we propose the following hypothesis: the CCR6/Mip-3α axis may be involved in the pathogenesis of AS, and block the CCR6/Mip-3α axis possibly inhibits its development. To this end, we will use the apoE-/- mouse model and the CCR6-/-apoE-/- double knockout mouse model (already established in our group) to investigate the role of CCR6/Mip-3α axis in the AS pathogenesis and its molecular mechanism. The confirmation of the CCR6/Mip-3α axis hypothesis in AS may improve our understanding in the pathomechanisms and help to develop potential drug therapeutic targets.