Infiltration of T Cells into a Three-Dimensional Psoriatic Skin Model Mimics Pathological Key Features

Int J Mol Sci. 2019 Apr 3;20(7):1670. doi: 10.3390/ijms20071670.

Abstract

Psoriasis is an autoimmune chronic dermatosis that is T cell-mediated, characterized by epidermal thickening, aberrant epidermal differentiation and inflammatory infiltrates, with a dominant Th1 and Th17 profile. Additional in vitro models are required to study the complex interactions between activated T cells and skin cells, and to develop new, more effective treatments. We have therefore sought to model this psoriatic inflammation by the generation of tissue-engineered immunocompetent tissues, and we have investigated the response of activated T-cell infiltration in models produced with lesional psoriatic skin cells on major hallmarks of psoriasis. The immunocompetent lesional skin model displayed a delayed onset of epidermal differentiation, an hyperproliferation of the basal keratinocytes, a drastic increase in the secretion of proinflammatory cytokines, and a disturbed expression of key transcription factors, as observed in lesional plaques, suggesting a crucial importance of combining the pathological phenotype of cutaneous cells to T cells in order to generate a relevant model for psoriasis. Finally, we found this skin model to be responsive to methotrexate treatment, making it a valuable tool for drug development.

Keywords: 3D model; T cells; adaptive immunity; inflammation; psoriasis; tissue engineering.

MeSH terms

  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation
  • Dermis / immunology
  • Dermis / pathology
  • Epithelium / drug effects
  • Epithelium / pathology
  • Female
  • Humans
  • Immunocompetence
  • Inflammation / pathology
  • Inflammation Mediators / metabolism
  • Keratinocytes / pathology
  • Lymphocyte Activation / immunology
  • Male
  • Methotrexate / pharmacology
  • Middle Aged
  • Models, Biological*
  • Phenotype
  • Psoriasis / immunology*
  • Psoriasis / pathology*
  • Signal Transduction
  • Skin / immunology*
  • Skin / pathology*
  • T-Lymphocytes / immunology*

Substances

  • Inflammation Mediators
  • Methotrexate