title: Modeling the role of TGF-β in regulation of the Th17 phenotype in the LPS-driven immune system.
abstract: 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.
authors.affiliation: Department of Mathematics, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Seongwon
authors.initials: S
authors.lastname: Lee
authors.forename: Hyung Ju
authors.initials: HJ
authors.lastname: Hwang
authors.forename: Yangjin
authors.initials: Y
authors.lastname: Kim
mesh_terms: D001249:Asthma / Q000276:immunology*; D003198:Computer Simulation; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology*; D018448:Models, Immunological; D010641:Phenotype; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology
chemical_list: D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta