炎症小体基因多态性在长寿人群免疫衰老中作用的研究

炎症小体(inflammasome)为nod-样受体蛋白(nod-like receptor proteins, NLRPs)参与组装而成的多聚蛋白复合体，是天然免疫的重要组成部分，介导促炎、抗炎反应及细胞焦亡(pyroptosis)。炎症小体基因多态性与多种老年病密切相关，故我们推测健康长寿人群可能存在不同的多态性格局及免疫衰老模式。本研究拟应用TaqMan技术对广西红水河流域长寿人群41个与免疫及老年病相关的炎症小体基因单核苷酸多态(SNPs)进行分型，并检测血清IL-1b、IL-18等焦亡相关的炎性因子水平及免疫功能状态，分析这些SNPs与炎性因子及免疫指标之间的交互作用及对免疫衰老的影响。本研究首次在缺乏免疫接种的自然长寿人群中检测炎症小体基因变异及血清焦亡相关因子水平，有望了解该人群的固有免疫基因的进化格局及其对天然免疫的影响，研究结果将对人类免疫衰老学说提供重要的遗传学数据。

Inflammasomes are a group of multi-protein complexes mainly consisted of nod-like receptor proteins (NLRPs). They play very important roles in innate immune by mediating pro- and anti-inflammatory responses and cellular pyroptosis. Variants on inflammasome genes have been linked to several aged-related disorders, we thus hypothesize that individuals who have successfully aged may be endowed unique polymorphism profiles and different immunosenescence patterns. In the current study, we aim to genotype 41 candidate immune- and aged-related single nucleotide polymorphisms on inflammasome genes with TaqMan technique for a long-lived cohort living in Guangxi Hongshuihe River Basin, to measure the serum levels of pyroptosis-related cytokines including IL-1beta and IL-18 as well as immunological profiles such as IgG and T-cell subsets, then analyze the potential interactions among these parameters and their plausible impacts on immunosenescence. To our knowledge, this is the first study to explore the genetic variants on inflammasome genes and their possible interplay with serum pyroptotic associated cytokines in long-lived individuals who received no vaccinations but naturally and successfully aged, hoping to have more understanding on the evolutionary profiles of innate immune genes and their potential influences on natural immune status for this healthy aging cohort. The results of this study will add important genetic data to human immunosenesence hypothesis.