Department of Dermatology, Columbia University Medical Center, NY, New York, USA.
Department of Dermatology, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
Sci Rep. 2020 Mar 5;10(1):4123. doi: 10.1038/s41598-020-60275-0.
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.
目前，炎症性皮肤病的药物筛选研究使用的模型系统只能部分重现人类病变皮肤。在这里，我们开发了一种将 T 细胞纳入人 3D 皮肤构建体（HSCs）的新策略，这使我们能够密切监测和定量 T 细胞反应。我们发现表皮促进 T 细胞的激活和浸润，并为其向表皮的选择性迁移提供定向信号。我们通过将极化的 Th1/Th17 细胞或源自银屑病患者的 CCR6+CLA+T 细胞纳入构建体中，建立了银屑病 HSC（pHSC）。这些 pHSCs 表现出银屑病表皮表型和特征性细胞因子谱，并对各种类别的银屑病药物产生反应，突出了我们模型作为药物筛选平台的潜在用途。总之，我们开发了一种先进的免疫活性 3D 皮肤模型，以研究表皮-T 细胞相互作用，并在人类相关和患者特异性背景下了解炎症性皮肤病的病理生理学。
