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

Scientific Reports
Jung U ShinAngela Christiano

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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Citations

Jan 3, 2021·Cellular and Molecular Life Sciences : CMLS·Inna S AfoninaRudi Beyaert
Jul 25, 2021·International Journal of Molecular Sciences·Charles Gwellem AnchangAndreas Ramming

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Methods Mentioned

BETA
flow cytometry
ELISA
bioprinting
PCR
FCS

Software Mentioned

Applied
Biosystems 7500

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