CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
我们的工作确立了CD81作为连接放射抵抗与免疫逃逸的关键桥梁,其通过维持GBM中CD274的丰度发挥作用,并突显CD81作为优化放射免疫治疗的有前景的治疗靶点。
英文原题:Umbilical Cord Mesenchymal-Stem-Cell-Derived Exosomes Exhibit Anti-Oxidant and Antiviral Effects as Cell-Free Therapies.
本研究为 ucMSC-EXO 在抗氧化应激和抗病毒效应方面提供了一种有前景的治疗策略,这为拓展 ucMSC-EXO 在无细胞治疗中的功能提供了见解。
活性氧(ROS)积累导致的氧化应激可引起细胞衰老和死亡。此外,骨骼肌在炎症性肌肉疾病中通常存在肠道病毒持续感染。脐带间充质干细胞(ucMSC)来源外泌体是具有良好生物活性的产物,已证明安全、免疫原性低,并具有潜在无细胞治疗功能。本研究分离并表征ucMSC来源外泌体(ucMSC-EXO)。在过氧化氢(H2O2)诱导的皮肤成纤维细胞(HSF)氧化损伤模型中,ucMSC-EXO可明显修复受损HSF。此外,ucMSC-EXO抑制丝裂原活化蛋白激酶(MAPK)、c-Jun氨基末端激酶(JNK)和核因子κB(NF-κB)信号通路,促进p21蛋白表达、降低核纤层蛋白B1表达,最终减轻氧化应激诱导的细胞损伤和衰老。在肠道病毒71型(EV71)和柯萨奇病毒B3(CVB3)感染横纹肌肉瘤(RD)细胞的模型中,ucMSC-EXO增强干扰素刺激基因15(ISG15)和ISG56表达,抑制肠道病毒复制,继而减少病毒诱导的促炎因子产生。本研究提出了ucMSC-EXO用于抗氧化应激和抗病毒治疗的有前景策略,并为扩展其无细胞治疗功能提供了思路。
The oxidative stress induced by the accumulation of reactive oxygen species (ROS) can lead to cell aging and death. Equally, the skeletal muscle usually hosts enteroviral persistent infection in inflammatory muscle diseases. As excellent bioactive products, the exosomes derived from umbilical cord mesenchymal stem cells (ucMSCs) have been proven to be safe and have low immunogenicity with a potential cell-free therapeutic function. Here, exosomes derived from ucMSCs (ucMSC-EXO) were extracted and characterized. In a model of oxidative damage to skin fibroblasts (HSFs) under exposure to H 2 O 2 , ucMSC-EXO had an observable repairing effect for the HSFs suffering from oxidative damage. Furthermore, ucMSC-EXO inhibited mitogen-activated protein kinases (MAPK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-B (NF- B) signaling pathways, thereby promoting p21 protein expression while decreasing lamin B1 protein expression, and finally alleviated oxidative stress-induced cell damage and aging. In a model of rhabdomyosarcoma (RD) cells being infected by enterovirus 71 (EV71) and coxsackievirus B3 (CVB3), the ucMSC-EXO enhanced the expression of interferon-stimulated gene 15 (ISG15) and ISG56 to inhibit enteroviral replication, whereafter reducing the virus-induced proinflammatory factor production. This study provides a promising therapeutic strategy for ucMSC-EXO in anti-oxidative stress and antiviral effects, which provides insight into extending the function of ucMSC-EXO in cell-free therapy.
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