Recapitulating T cell infiltration in 3D psoriatic skin models for patient-specific drug testing

Sci Rep. 2020 Mar 5;10(1):4123. doi: 10.1038/s41598-020-60275-0.

Abstract

Drug screening studies for inflammatory skin diseases are currently performed using model systems that only partially recapitulate human diseased skin. Here, we developed a new strategy to incorporate T cells into human 3D skin constructs (HSCs), which enabled us to closely monitor and quantitate T cell responses. We found that the epidermis promotes the activation and infiltration of T cells into the skin, and provides a directional cue for their selective migration towards the epidermis. We established a psoriatic HSC (pHSC) by incorporating polarized Th1/Th17 cells or CCR6+CLA+ T cells derived from psoriasis patients into the constructs. These pHSCs showed a psoriatic epidermal phenotype and characteristic cytokine profiles, and responded to various classes of psoriasis drugs, highlighting the potential utility of our model as a drug screening platform. Taken together, we developed an advanced immunocompetent 3D skin model to investigate epidermal-T cell interactions and to understand the pathophysiology of inflammatory skin diseases in a human-relevant and patient-specific context.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblasts / cytology
  • Fibroblasts / immunology
  • Fibroblasts / metabolism
  • Flow Cytometry
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • Psoriasis / immunology*
  • Real-Time Polymerase Chain Reaction
  • Receptors, CCR6 / genetics
  • Receptors, CCR6 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / cytology*
  • Skin / immunology
  • Skin / metabolism*
  • Th1 Cells / metabolism
  • Th17 Cells / metabolism

Substances

  • CCR6 protein, human
  • Cytokines
  • Receptors, CCR6