title: Modelling epidermis homoeostasis and psoriasis pathogenesis.
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.
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Shanghai 200031, People's Republic of China Naval Submarine Academy, Qingdao, Shandong 266000, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Shanghai 200031, People's Republic of China.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Hou
authors.affiliation: Sprim Advanced Life Sciences, 1 Daniel Burnham Court, San Francisco, CA 94109, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Henrot
authors.affiliation: LVMH Research, 185 Avenue de Verdun, Saint-Jean-de-Braye 45804, France.
authors.forename: Sylvianne
authors.initials: S
authors.lastname: Schnebert
authors.affiliation: LVMH Research, 185 Avenue de Verdun, Saint-Jean-de-Braye 45804, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Dumas
authors.affiliation: LVMH Research, 185 Avenue de Verdun, Saint-Jean-de-Braye 45804, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Heusèle
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Shanghai 200031, People's Republic of China jinyang2004@gmail.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
mesh_terms: D004817:Epidermis; D006706:Homeostasis; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D010789:Phototherapy; D011565:Psoriasis / Q000378:metabolism* / Q000503:physiopathology* / Q000628:therapy
keywords: bimodal switch; epidermal homoeostasis; immune system; mathematical model; psoriasis