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

Research output: Contribution to journalArticle

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

Original languageEnglish
Article number4123
JournalScientific Reports
Volume10
Issue number1
DOIs
Published1 Dec 2020

King's Authors

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.

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