Development of a dynamic mathematical model of epidermis reveals critical importance of increasing the proportion of both cycling stem and transient amplifying cells, in the development of psoriatic plaques

Mathematic modelling allows exploration of the contribution of specific quantifiable parameters to processes such as epidermal homeostasis. We created a stochastic agent-based model which combines known kinetic parameters with histological features characteristic of normal and psoriatic epidermis. Iterative stimulation of the model allowed rigorous testing and establishment of robust boundaries including analysis of cell cycle time and the proportion of cells dividing, within which the model remained stable. In contrast to adjusting cell cycle times, the model showed a critical role for an initiating «cytokine» stimulus and a resulting increase in the proportion of actively dividing stem cells and the number of rounds of transient amplifying (TA) cell division within 'uninvolved' epidermis. The model showed excellent concordance with existing data including an absolute increase in both the proliferative and differentiating compartments and a reduction in both total epidermal turnover time and transit time of differentiating cells. Adjusting cell cycle length within defined boundaries had no significant impact on the model. Importantly, the model remained stable and became independent of a continuous cytokine stimulus through production of «autocrine» factors. In summary, we have developed a stochastic model of epidermal homeostasis which has allowed us to create for the first time an in silico model of psoriasis development. The model has the potential to provide insight into psoriatic plaque development and the impact of treatment modalities.1 page(s