Immunology-Oncology Research Axis, Maisonneuve-Rosemont Hospital Research Centre, Montreal, QC, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada.
Sci Rep. 2023 Feb 3;13(1):1967. doi: 10.1038/s41598-023-28625-w.
Dendritic cells (DCs) patrol the organism at an immature stage to detect the presence of pathogens. Once activated, these mature DCs reach the lymph nodes to activate antigen-specific T lymphocytes and thus initiate an adaptative immune response to control the pathogen. The migration of both immature and mature DCs is a key process for their optimal function. DC migration requires transit through narrow constrictions that is allowed by their high local and global deformation capabilities. In addition to cytoplasmic changes, the nucleus mechanical properties also have a major impact for cellular migration and motility. Yet, nucleus intracellular mobility of dendritic cells or its variation upon maturation have not been investigated. Our study defines the biophysical phenotypic variations of dendritic cells upon maturation using interferometric deformability cytometry. This method characterizes different cellular mechanical properties, such as elongation and nucleus offset, by assessing the refractive index spatial distribution of shear-induced deformed cells. By using these parameters, our data suggest that in vitro bone marrow derived dendritic cell (BMDC) maturation induces cell stiffening and reduces nucleus mobility, allowing to distinguish immature and mature dendritic cells. Overall, our method provides insights on intracellular mechanical properties of two dendritic cell states.
树突状细胞(DCs)在不成熟阶段在体内巡逻,以检测病原体的存在。一旦被激活,这些成熟的 DC 会到达淋巴结,激活抗原特异性 T 淋巴细胞,从而引发适应性免疫反应来控制病原体。未成熟和成熟 DC 的迁移是其发挥最佳功能的关键过程。DC 的迁移需要通过狭窄的限制来进行,这是由它们高局部和全局变形能力所允许的。除了细胞质的变化,核的力学特性也对细胞迁移和运动有重大影响。然而,树突状细胞的核内迁移或其成熟时的变化尚未得到研究。我们的研究使用干涉变形细胞术定义了树突状细胞成熟时的生物物理表型变化。该方法通过评估剪切诱导变形细胞的折射率空间分布来表征不同的细胞力学特性,如伸长和核偏移。通过使用这些参数,我们的数据表明,体外骨髓来源的树突状细胞(BMDC)成熟会诱导细胞变硬,并降低核的流动性,从而能够区分未成熟和成熟的树突状细胞。总的来说,我们的方法提供了对两种树突状细胞状态的细胞内力学特性的深入了解。