Dynamical Analysis of the Regulatory Network Controlling Natural Killer Cells Differentiation

Many disease fighting strategies have focused on the generation of NK cells, since they constitute the main immune barrier against cancer and intracellular pathogens such as viruses. Therefore, a predictive model for the development of NK cells would constitute a useful tool to test several hypotheses regarding the production of these cells during both physiological and pathological conditions. Here, we present a boolean network model that reproduces experimental results reported on the literature regarding the progressive stages of the development of NK cells in wild-type and mutant backgrounds. The model allows for the simulation of different conditions, including extracellular micro-environment as well as the simulation of genetic alterations. It also describes how NK cell differentiation depends on a molecular regulatory network that controls the specification of lymphoid lineages, such as T and B cells, which share a common progenitor with NKs. Furthermore, the study shows that the structure of the regulatory network strongly determines the stability of the expression patterns against perturbations.