A multi-scale model of dendritic cell education and trafficking in the lung: implications for T cell polarization

Health Sciences face a significant challenge in translating basic science data into improved understanding of innate and adaptive immunity. To improve understanding of the dynamic role of dendritic cells in the lung, a mathematical model was developed using a physiologically structured framework that explicitly accounts for functional heterogeneity. As sentinels of the immune system, dendritic cells play critical roles in coupling innate to adaptive immunity and produce an important immune regulatory cytokine: IL-12. The term IL-12 actually refers to the net bioactivity of three related proteins; IL12p40, IL12p70, and IL12(p40)2; assembled from two independent gene products: p35 and p40. The model for dendritic cell education and trafficking was created by incorporating five dimensions: chronological time, maturational age, p35 signal, p40 signal, and spatial location. The computational framework was calibrated to and validated against appropriate experimental studies. Using this validated model, I explore the impact of dynamic changes in the lung epithelium of IL-4, IFN-gamma, and PGE2 on the dynamic ability of dendritic cells to polarize T cell subsets. In summary, this multi-scale model provides an essential aid in understanding the impact of a dynamically changing lung microenvironment on the ability of dendritic cells to orchestrate adaptive immunity.