RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:PIEZO1 in Immune Cells: From Force to Function.
PIEZO1 in Immune Cells: From Force to Function.
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作为一种专业的机械传感器,PIEZO1将机械刺激——如基底硬度、流体剪切应力和膜张力——转化为细胞内钙内流,进而调控广泛的免疫过程。本章详细阐述了其在固有免疫和适应性免疫中的重要意义,包括T细胞活化和迁移、巨噬细胞极化、树突状细胞活化、NK 细胞细胞毒性、中性粒细胞胞外诱捕网(NET)形成以及B细胞抗原识别和向IgA的类别转换。PIEZO1作为一个核心调控因子,通过整合来自细胞微环境的信号来精细调节免疫应答,影响炎症、病原体清除和代谢重编程。尽管取得了这些进展,关于其在慢性疾病、自身免疫和癌症免疫中的作用仍存在关键问题。靶向PIEZO1为机械应力和免疫功能障碍驱动的疾病(如纤维化、动脉粥样硬化和实体瘤)提供了一种有前景的治疗策略,可能开启机械免疫治疗的新时代。
As a professional mechanosensor, PIEZO1 converts mechanical stimuli-such as substrate stiffness, fluid shear stress, and membrane tension-into intracellular calcium influx, which in turn regulates a wide array of immune processes. The chapter details its significance across both innate and adaptive immunity, including T cell activation and migration, macrophage polarization, dendritic cell activation, natural killer cell cytotoxicity, neutrophil extracellular trap (NET) formation, and B cell antigen discrimination and class-switching to IgA.
PIEZO1 emerges as a central regulator that fine-tunes immune responses by integrating signals from the cellular microenvironment, influencing inflammation, pathogen clearance, and metabolic reprogramming. Despite these advances, key questions remain regarding its role in chronic disease, autoimmunity, and cancer immunity.
Targeting PIEZO1 presents a promising therapeutic strategy for conditions driven by mechanical stress and immune dysfunction, such as fibrosis, atherosclerosis, and solid tumours, potentially inaugurating a new era of mechano-immunotherapy.
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