PDF(Pubmed)
Abstract：
In this study, we provide a dynamical systems perspective to the modelling of pathological states induced by tumors or infection. A unified disease model is established using the innate immune system as the reference point. We propose a two-layer network model for carcinogenesis and sepsis based upon the interaction of parenchymal cells and immune cells via cytokines, and the co-evolutionary dynamics of parenchymal, immune cells, and cytokines. Our aim is to show that the complex cellular cooperation between parenchyma and stroma (immune layer) in the physiological and pathological case can be qualitatively and functionally described by a simple paradigmatic model of phase oscillators. By this, we explain carcinogenesis, tumor progression, and sepsis by destabilization of the healthy homeostatic state (frequency synchronized), and emergence of a pathological state (desynchronized or multifrequency cluster). The coupled dynamics of parenchymal cells (metabolism) and nonspecific immune cells (reaction of innate immune system) are represented by nodes of a duplex layer. The cytokine interaction is modeled by adaptive coupling weights between the nodes representing the immune cells (with fast adaptation time scale) and the parenchymal cells (slow adaptation time scale) and between the pairs of parenchymal and immune cells in the duplex network (fixed bidirectional coupling). Thereby, carcinogenesis, organ dysfunction in sepsis, and recurrence risk can be described in a correct functional context.
摘要：
在这项研究中,我们为肿瘤或感染引起的病理状态的建模提供了动态系统的观点。以先天免疫系统为参照点,建立统一的疾病模型。我们基于实质细胞和免疫细胞通过细胞因子的相互作用，提出了一个用于癌变和败血症的两层网络模型。和实质的共同进化动力学，免疫细胞，和细胞因子。我们的目的是表明，在生理和病理情况下，薄壁组织和基质（免疫层）之间的复杂细胞合作可以通过简单的相位振荡器模型在质量和功能上进行描述。通过这个，我们解释致癌作用，肿瘤进展，和败血症通过健康体内平衡状态的不稳定(频率同步)，和出现病理状态（去同步或多频率簇）。实质细胞（代谢）和非特异性免疫细胞（先天免疫系统的反应）的耦合动力学由双链层的节点表示。细胞因子相互作用通过表示免疫细胞(具有快速适应时间尺度)和实质细胞(缓慢适应时间尺度)的节点之间以及双链网络中的实质细胞和免疫细胞对之间的自适应耦合权重(固定双向耦合)来建模。因此，致癌作用，脓毒症的器官功能障碍，复发风险可以在正确的功能背景下描述。
