Modeling the Role of TGF-β in Regulation of the Th17 Phenotype in the LPS-Driven Immune System
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- 作者：Seongwon Lee (1)
Hyung Ju Hwang (1)
Yangjin Kim (2) (3) - 关键词：Lipopolysaccharide ; Th17 ; TGF ; Beta ; Mathematical model
- 刊名：Bulletin of Mathematical Biology
- 出版年：2014
- 出版时间：May 2014
- 年：2014
- 卷：76
- 期：5
- 页码：1045-1080
- 全文大小：
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Hyung Ju Hwang (1)
Yangjin Kim (2) (3)
1. Department of Mathematics, Pohang University of Science and Technology, Pohang, Republic of Korea
2. Department of Mathematics, Konkuk University, Seoul, 143-701, Republic of Korea
3. Department of Mathematics, Ohio State University, Columbus, OH, 43210, USA - ISSN：1522-9602
文摘
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.