Investigations on T cell transmigration in a human skin-on-chip (SoC) model.
炸薯条
计算机科学
作者
Xiaoou Ren,Anthony E. Getschman,Samuel T Hwang,Brian F. Volkman,Thomas Klonisch,David B. Levin,Min Zhao,Susy Santos,Song Liu,Jasmine Cheng,Francis Lin
出处
期刊:Lab on a Chip [The Royal Society of Chemistry] 日期:2021-04-20卷期号:21 (8): 1527-1539被引量:5
标识
DOI:10.1039/d0lc01194k
摘要
A microfluidics-based three-dimensional skin-on-chip (SoC) model is developed in this study to enable quantitative studies of transendothelial and transepithelial migration of human T lymphocytes in mimicked skin inflammatory microenvironments and to test new drug candidates. The keys results include 1) CCL20-dependent T cell transmigration is significantly inhibited by an engineered CCL20 locked dimer (CCL20LD), supporting the potential immunotherapeutic use of CCL20LD for treating skin diseases such as psoriasis; 2) transepithelial migration of T cells in response to a CXCL12 gradient mimicking T cell egress from the skin is significantly reduced by a sphingosine-1-phosphate (S1P) background, suggesting the role of S1P for T cell retention in inflamed skin tissues; and 3) T cell transmigration is induced by inflammatory cytokine stimulated epithelial cells in the SoC model. Collectively, the developed SoC model recreates a dynamic multi-cellular micro-environment that enables quantitative studies of T cell transmigration at a single cell level in response to physiological cutaneous inflammatory mediators and potential drugs.