Modelling epidermis homoeostasis and psoriasis pathogenesis

Authored by Hong Zhang, Wenhong Hou, Laurence Henrot, Sylvianne Schnebert, Marc Dumas, Catherine Heusele, Jin Yang

Date Published: 2015

DOI: 10.1098/rsif.2014.1071

Sponsors: No sponsors listed

Platforms: No platforms listed

Model Documentation: Other Narrative Mathematical description

Model Code URLs: Model code not found

Abstract

We present a computational model to study the spatio-temporal dynamics of epidermis homoeostasis under normal and pathological conditions. The model consists of a population kinetics model of the central transition pathway of keratinocyte proliferation, differentiation and loss and an agent-based model that propagates cell movements and generates the stratified epidermis. The model recapitulates observed homoeostatic cell density distribution, the epidermal turnover time and the multilayered tissue structure. We extend the model to study the onset, recurrence and phototherapy-induced remission of psoriasis. The model considers psoriasis as a parallel homoeostasis of normal and psoriatic keratinocytes originated from a shared stem cell (SC) niche environment and predicts two homoeostatic modes of psoriasis: a disease mode and a quiescent mode. Interconversion between the two modes can be controlled by interactions between psoriatic SCs and the immune system and by normal and psoriatic SCs competing for growth niches. The prediction of a quiescent state potentially explains the efficacy of multi-episode UVB irradiation therapy and recurrence of psoriasis plaques, which can further guide designs of therapeutics that specifically target the immune system and/or the keratinocytes.

Tags

progenitor cells Transit-amplifying cells Human stratum corneum Normal human-skin Stem-cells Multicellular systems Regional differences Clinical-features Uvb phototherapy Self-renewal