Modelling of indirect cell-cell interaction networks mediated by IFNy /IL-4 cytokine involved in atopic dermatitis

Atopic dermatitis (AD) is an immune-driven inflammatory skin disease that is known to have a significantly high life-time prevalence in the human population. T-helper (Th) immune cells play a key role in the pathogenesis of AD which is marked by defects in the skin barrier function along with a significant increase in the population of either Th1 or Th2 sub-types of Th cells. The progression of AD from the acute to chronic phase is still poorly understood, and here we explore the mechanism of this transition through the study of a mathematical model for indirect cell-cell interactions among Th and skin cells via the secreted cytokines IFNy and IL-4, both known to have therapeutic potential. An increase in the level of cytokine IFN y can catalyse the transition of AD from an acute to a chronic stage, while an increase in the level of cytokine IL-4 has the reverse effect. In our model, the transition of AD from the acute to chronic stage and vice versa can be abrupt (switch-like) with hysteresis: this bistable behaviour can potentially be used to keep AD in the acute phase since therapy based on suppression of IFNy can retard the transition to the chronic phase.

Automated summary

Atopic dermatitis (AD) is an immune-driven inflammatory skin disease with a high prevalence in the human population. The transition from acute to chronic phase of AD is still poorly understood. A mathematical model suggests that increasing the level of cytokine IFNy can catalyze the transition to chronic phase, while increasing the level of cytokine IL-4 has the opposite effect. This bistable behavior can potentially be used to keep AD in the acute phase through therapy targeting IFNy.