膜的背包的机械刚性调节了树突细胞和巨细胞的先天免疫功能
He Liu1, Zhan Liu2, Xuying Hu3
1State Key Laboratory of Radiation Medicine and Protection, The Fourth Affiliated Hospital of Soochow University, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China; Institute of Biomedical Engineering, School of Life Sciences, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, China.
具有可调节硬度的工程细胞背包重新编程了免疫细胞,增强了抗瘤反应. 这一突破推动了免疫疗法的先天性免疫细胞工程.
科学领域:
- 生物材料科学 生物材料科学
- 免疫学 免疫学 免疫学
- 细胞机械生物学 细胞机械生物学
背景情况:
- 细胞背包提供了通过机械转导进行先天免疫细胞工程的潜力.
- 背包硬度与免疫细胞功能之间的关系需要在机械免疫学中进行进一步的研究.
研究的目的:
- 制造和表征可以调整硬度的,耐细胞化细胞背包.
- 探索背包硬度对先天性免疫细胞功能和机械传导的影响.
- 阐明潜在的分子机制,并评估体内治疗疗效.
主要方法:
- 使用丝纤维素和聚 (乳酸-co-糖酸) 制造带有膜的背包,具有可调节的刚度 (5 kPa,500 kPa,50 MPa).
- 化学修饰以有效地 (>70%) 结合到骨髓衍生的树突细胞和巨细胞.
- 在B16F10黑色素瘤模型中评估免疫细胞表型,细胞因子分泌,T细胞激活,Hippo通路信号和抗瘤效应.
主要成果:
- 高刚度 (50 MPa) 的背包显著增强了树突细胞成熟和巨细胞两极分化.
- 观察到增高的促炎性细胞因子 (TNF-α,IL-6) 的分泌和改善的CD8+ T细胞激活.
- 高刚度的背包通过通过actin聚合介导机械感知促进YAP核转位来抑制Hippo路径.
- 在体内,背包携带的免疫细胞抑制了瘤生长,改善了存活率,并增强了细胞毒性T细胞反应和免疫记忆.
结论:
- 可调节硬度的细胞背包是设计天生的免疫细胞的强大平台.
- 这项研究阐明了免疫治疗设计的关键结构-功能关系和机制传导途径.
- 这些发现为新型免疫疗法铺平了道路,利用机械线索进行免疫细胞重编程.
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