089 3D Computational Modelling of Immune Interaction and Epidermal Homeostasis in Psoriasis

Psoriasis is a chronic inflammatory skin disease characterised by immune cytokine stimulated epidermal hyperproliferation. Previous modelling studies of psoriatic have been limited to 2D models and lacked cell-cell interactions. We developed the first 3D agent-based model cell dynamics gain insights into complex spatio-temporal changes, in particular how stimuli induces hyperproliferation altering division structure psoriasis. The was implemented state-of-art LAMMPS open-source, massively parallel simulator. Extracellular calcium, endogenous growth factors cytokines are represented as continuum fields, while keratinocytes (stem, transit-amplifying (TA), differentiated cells), T cells basement membrane (BM) discrete particles. Each has set attributes (growth rate, probability, position, etc) whose values governed processes including 1) Monod-based cellular 2) Probability-based based on calcium concentration 3) Contact adhesion forces regulate layer formation 4) Diffusion-reaction for spatial distribution fields. 2 steady states, healthy (non-lesional) (lesional) skin. Transition from state triggered temporary stimulus. validated against population ratios stem, TA, differentiated, cells, cycle turnover times vivo. simulates structural properties epidermis, stratification, wave-like rete ridges, change height length ridges normal psoriatic. Spatial regulation ensure that divide along BM zone. Finally, different scenarios can be simulated delineating psoriasis response duration. Future will include treatment effects, with comparison patient data predict outcomes.