HOPF BIFURCATION IN A MODEL OF TGF-β IN REGULATION OF THE TH 17 PHENOTYPE.

Airway exposure of lipopolysaccharide (LPS) is shown to regulate type I and type II helper T cell induced asthma. While high doses of LPS derive Th1-or Th17-immune responses, low LPS levels lead to Th2 responses. In this paper, we analyze a mathematical model of Th1/Th2/Th17 asthma regulation suggested by Lee et al. (S. Lee, H.J. Hwang, and Y. Kim, Modeling the role of TGF-fi in regulation of the Th17 phenotype in the LPS-driven immune system, Bull Math Biol., 76 (5), 1045-1080, 2014) and show that the system can undergo a Hopf bifurcation at a steady state of the Th17 phenotype for high LPS levels in the presence of time delays in inhibition pathways of two key regulators: IL-4/Th2 activities (H) and TGF-β levels (G). The time delays affect the phenotypic switches among the Th1, Th2, and Th17 phenotypes in response to time-dependent LPS doses via nonlinear crosstalk between H and G. An extended reaction-diffusion model also predicts coexistence of these phenotypes under various biochemical and bio-mechanical conditions in the heterogeneous microenvironment. [ABSTRACT FROM AUTHOR]