Recapitulating T cell infiltration in 3D psoriatic skin models for patient-specific drug testing
Authors
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
Institution
Columbia University, New York
Country
United States
Year
2020
Journal
Scientific Reports
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.