Lee Seongwon, Hwang Hyung Ju, Kim Yangjin
Department of Mathematics, Pohang University of Science and Technology, Pohang, Republic of Korea.
Bull Math Biol. 2014 May;76(5):1045-80. doi: 10.1007/s11538-014-9946-6. Epub 2014 Mar 8.
Airway exposure levels of lipopolysaccharide (LPS) are known to determine type I versus type II helper T cell induced experimental asthma. While low doses of LPS derive Th2 inflammatory responses, high (and/or intermediate) LPS levels induce Th1- or Th17-dominant responses. The present paper develops a mathematical model of the phenotypic switches among three Th phenotypes (Th1, Th2, and Th17) in response to various LPS levels. In the present work, we simplify the complex network of the interactions between cells and regulatory molecules. The model describes the nonlinear cross-talks between the IL-4/Th2 activities and a key regulatory molecule, transforming growth factor β (TGF-β), in response to high, intermediate, and low levels of LPS. The model characterizes development of three phenotypes (Th1, Th2, and Th17) and predicts the onset of a new phenotype, Th17, under the tight control of TGF-β. Analysis of the model illustrates the mono-, bi-, and oneway-switches in the key regulatory parameter sets in the absence or presence of time delays. The model also predicts coexistence of those phenotypes and Th1- or Th2-dominant immune responses in a spatial domain under various biochemical and bio-mechanical conditions in the microenvironment.
已知气道中脂多糖（LPS）的暴露水平决定了I型与II型辅助性T细胞诱导的实验性哮喘。低剂量的LPS会引发Th2炎症反应，而高（和/或中）剂量的LPS水平则会诱导以Th1或Th17为主导的反应。本文建立了一个数学模型，用于描述三种Th表型（Th1、Th2和Th17）在不同LPS水平下的表型转换。在本研究中，我们简化了细胞与调节分子之间相互作用的复杂网络。该模型描述了在高、中、低水平LPS刺激下，IL-4/Th2活性与关键调节分子转化生长因子β（TGF-β）之间的非线性相互作用。该模型表征了三种表型（Th1、Th2和Th17）的发展，并预测了在TGF-β严格调控下新表型Th17的出现。对该模型的分析揭示了在不存在或存在时间延迟的情况下，关键调节参数集中的单开关、双开关和单向开关。该模型还预测了在微环境中各种生化和生物力学条件下，这些表型与Th1或Th2主导的免疫反应在空间域中的共存情况。
