小胶质细胞（MI）激活为核心的脑内过度炎症反应是帕金森病(PD)的重要病理特征，而外周免疫对中枢炎症影响深刻：一次大剂量LPS腹腔注射足以引起脑内持久的炎症反应，反之非甾体抗炎药物对外周免疫的抑制也能降低PD的发病率。外周血单核细胞（PBM）是外周影响中枢的重要途径，它能穿越血脑屏障入脑演变成MI直接或间接参与中枢炎症反应，而PBM在外周的免疫状态直接影响其入脑后对脑内炎症的干预方向。免疫耐受指抗原持续存在时发生的免疫下调或不应答，可以避免免疫系统的过度激活，是机体的一种自我保护机制。免疫耐受的PBM能够对中枢炎症施加影响，使其受限下调。有研究显示尽管PD患者的外周血中具备诱导免疫耐受的条件，但其外周免疫仍处于异常激活状态，据此我们提出外周PBM的免疫耐受障碍是PD脑内炎症不能及时下调的重要原因。本课题拟明确PBM免疫耐受对脑内炎症和PD发病的影响。为通过外周途径探讨PD提供思路。

Neuroinflammation is an important pathogenesis of Parkinson's Disease (PD). Peripheral immune system used to exert significant impact on immune activities in the brain. The peripheral blood monocytes or macrophages (PBM) influence the inflammation within brain by transforming into microglia after passing through blood brain barrier or forming a special group of macrophages in brain such as perivascular macrophages. Immune tolerance is the refractoriness of immune system to certain stimulations that exist within body continuously or repeatedly to avoid over-activation of immune cells and unnecessary by-stander injury. The most important part of the immune tolerance is the macrophages tolerance, which featured of immune downregulation, and may lead to chronic inflammation in multiple condtions when impaired. The minor dose of LPS (lipopolysacchride)given peripherally has been demonstrated to be neuroprotective or attenuate the brain inflammation in various brain injuries.The minimal dose of LPS is able to induce the macrophages tolerance. Suitable LPS concentration for tolerance induction is approved to exist in peripheral blood in PD patients, while the peripheral immune cells in PD patients are still acitvated,combining with the evidence from our previous study that CD200R in PBM from PD patient is abnormally regulated and CD200R takes an active role in immune tolerance, we thus propose that there is an impaired PBM tolerance in PD patients, which leads to the failure of downregulation of the brain inflammation.We try in this proposal to explore the influence of activated or tolerated PBM on brain inflammation, see its effect on PD occurrence by manipulating PBM immune state and the specific roles of CD200/CD200R pathway in the whole process concomitantly.Hoping to get closer to the pathogenesis of PD.