BioRxiv
bioRxiv Subject Collection: Systems Biology
This feed contains articles for bioRxiv Subject Collection "Systems Biology"
Distribution-modeling quantifies collective Th cell decision circuits in chronic inflammation
Immune responses are tightly regulated by a diverse set of interacting immune cell populations. Alongside decision-making processes such as differentiation into specific effector cell types, immune cells initiate proliferation at the beginning of an inflammation, forming two layers of complexity. Here, we developed a general mathematical framework for the data-driven analysis of collective immune-cell dynamics. We identified qualitative and quantitative properties of generic network motifs, and we specified differentiation dynamics by analysis of kinetic transcriptome data. Further, we derived a specific, data-driven mathematical model for Th1 vs. Tfh cell fate-decision dynamics in acute and chronic LCMV infections in mice. The model recapitulates important dynamical properties without model fitting, and solely by employing measured response-time distributions. Model simulations predict different windows of opportunity for perturbation in acute and chronic infection scenarios, with potential implications for optimization of targeted immunotherapy.
Burt, P., Thurley, K.
February 1, 2023
http://biorxiv.org/cgi/content/short/2023.01.29.526090v1?rss=1