Data set related to the article "The longevity-associated variant of BPIFB4 improves a CXCR4-mediated striatum-microglia crosstalk preventing disease progression in a mouse model of Huntington's disease"

This record contains row data related to the article "The longevity-associated variant of BPIFB4 improves a CXCR4-mediated striatum-microglia crosstalk preventing disease progression in a mouse model of Huntington's disease". The longevity-associated variant (LAV) of the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) has been found significantly enriched in long-living individuals. Neuroinflammation is a key player in Huntington's disease (HD), a neurodegenerative disorder caused by neural death due to expanded CAG repeats encoding a long polyglutamine tract in the huntingtin protein (Htt). Herein, we showed that striatal-derived cell lines with expanded Htt (STHdh Q^111/111) expressed and secreted lower levels of BPIFB4, when compared with Htt expressing cells (STHdh Q^7/7), which correlated with a defective stress response to proteasome inhibition. Overexpression of LAV-BPIFB4 in STHdh Q^111/111 cells was able to rescue both the BPIFB4 secretory profile and the proliferative/survival response. According to a well-established immunomodulatory role of LAV-BPIFB4, conditioned media from LAV-BPIFB4-overexpressing STHdh Q111^/111 cells were able to educate Immortalized Human Microglia-SV40 microglial cells. While STHdh Q^111/111 dying cells were ineffective to induce a CD163 + IL-10^high pro-resolving microglia compared to normal STHdh Q^7/7, LAV-BPIFB4 transduction promptly restored the central immune control through a mechanism involving the stromal cell-derived factor-1. In line with the in vitro results, adeno-associated viral-mediated administration of LAV-BPIFB4 exerted a CXCR4-dependent neuroprotective action in vivo in the R6/2 HD mouse model by preventing important hallmarks of the disease including motor dysfunction, body weight loss, and mutant huntingtin protein aggregation. In this view, LAV-BPIFB4, due to its pleiotropic ability in both immune compartment and cellular homeostasis, may represent a candidate for developing new treatment for HD.本数据集收录与论文"BPIFB4长寿相关变异体改善CXCR4介导的纹状体-小胶质细胞串扰并延缓亨廷顿病小鼠模型的疾病进展"相关的原始行数据。含杀菌/通透性增加折叠域家族B成员4（bactericidal/permeability-increasing fold-containing family B member 4, BPIFB4）的长寿相关变异体（longevity-associated variant, LAV）已被证实显著富集于长寿人群中。神经炎症是亨廷顿病（Huntington's disease, HD）的关键致病环节，该神经退行性疾病由亨廷顿蛋白（huntingtin protein, Htt）编码区CAG重复序列扩增，导致蛋白产物含过长聚谷氨酰胺肽段，进而引发神经元死亡所致。本研究发现，与表达正常亨廷顿蛋白的细胞系（STHdh Q^7/7）相比，携带扩增型亨廷顿蛋白的纹状体衍生细胞系（STHdh Q^111/111）的BPIFB4表达与分泌水平显著降低，且该现象与蛋白酶体抑制诱导的应激应答缺陷相关。在STHdh Q^111/111细胞中过表达LAV-BPIFB4，可同时恢复BPIFB4的分泌特征与细胞增殖/存活应答能力。基于LAV-BPIFB4已明确的免疫调节功能，过表达LAV-BPIFB4的STHdh Q^111/111细胞的条件培养基可诱导永生化人小胶质细胞-SV40（Immortalized Human Microglia-SV40）发生表型转变。正常STHdh Q^7/7细胞可诱导CD163⁺IL-10^high促消退型小胶质细胞生成，而STHdh Q^111/111凋亡细胞无此效应，但LAV-BPIFB4转导可通过涉及基质细胞衍生因子-1（stromal cell-derived factor-1）的机制快速恢复中枢免疫稳态。与体外实验结果一致，腺相关病毒介导的LAV-BPIFB4给药可在R6/2 HD小鼠模型中通过CXCR4依赖通路发挥神经保护作用，延缓亨廷顿病的核心病理特征，包括运动功能障碍、体重下降及突变亨廷顿蛋白聚集。综上，LAV-BPIFB4凭借其在免疫组分与细胞稳态维持中的多效性功能，有望成为亨廷顿病新型治疗策略的候选靶点。