Modeling the Epidermis Homeostasis and the Psoriasis

Abstract

The epidermis renewal and homeostasis is maintained by a multistage process including cell proliferation, differentiation, migration, apoptosis and desquamation. We present a computational model of the spatial-temporal dynamics of the epidermis. The model consists of a population kinetics model of the central transition pathway of keratinocyte proliferation, differentiation and loss and an agent-based cell migration model that propagates cell movements and generates the stratified epidermis. The model visualizes the epidermal renewal by embedding stochastic events of population kinetics into the cell migration events. The model reproduces observed cell density distribution and the epidermal turnover time. We apply the model to study the onset and phototherapy-induced remission of psoriasis. The model considers the psoriasis as a parallel homeostasis of normal and psoriatic keratinocytes originated from a shared stem cell niche environment and predicts two steady-state modes of the psoriasis: a disease mode and a quiescent mode. The bimodal psoriasis is established by the interaction between psoriatic stem cells and the immune system. The prediction of a quiescent state potentially explains the efficacy of the multi-episode UVB irradiation therapy and reoccurrence of psoriasis.