Qualitative modeling and analysis of the indoleamine 2,3-dioxygenase regulatory network in homeostasis and disease

Indoleamine 2,3-dioxygenase (IDO) has key role in immune regulation and it acts as a constituent of the inflammatory reaction allied with infection, allergic diseases, autoimmunity and cancer. IDO function as an immunosuppressive enzyme, which degrades the tryptophan into kynurenine and other downstream metabolites. Interferon gamma (IFN-γ) is a potent inducer of IDO. Transforming growth factor-beta (TGF-β) is the negative regulator of IDO. Both the TGF-β and IFN-γ have opposite effects on various cellular functions. IFN-γ and TGF-β inhibit the activity of each other through different pathways. In the pathological state when the homeostasis disturb, the impairment of IDO provides significant role in the pathogenesis of disease. The modeling of the Gene regulatory network (GRN) of IDO, IFN-γ and TGF-β using of René Thomas Formalism, help us in understanding their dynamical behaviors. We observe two types of steady states behaviors in this study. The cycle shows the homeostasis of IDO and TGF-β while IFN-γ is inactive (silent). The stable state shows the high expression levels of IFN-γ and IDO while TGF-β is silent. These findings recognized prospective novel targets for therapy in a range of clinical conditions, including, inflammation, tumor resistance and autoimmunity.