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

Jung U. Shin, Hasan E. Abaci*, Lauren Herron, Zongyou Guo, Brigitte Sallee, Alberto Pappalardo, Joanna Jackow, Eddy Hsi Chun Wang, Yanne Doucet, Angela M. Christiano

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

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.

Original languageEnglish
Article number4123
JournalScientific Reports
Volume10
Issue number1
Early online date5 Mar 2020
DOIs
Publication statusPublished - 5 Mar 2020

Fingerprint

Dive into the research topics of 'Recapitulating T cell infiltration in 3D psoriatic skin models for patient-specific drug testing'. Together they form a unique fingerprint.

Cite this