Investigations on T cell transmigration in a human skin-on-chip (SoC) model. Lab Chip 2021 Apr 20;21(8):1527-1539
Date
02/23/2021Pubmed ID
33616124Pubmed Central ID
PMC8058301DOI
10.1039/d0lc01194kScopus ID
2-s2.0-85104501502 (requires institutional sign-in at Scopus site) 55 CitationsAbstract
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.
Author List
Ren X, Getschman AE, Hwang S, Volkman BF, Klonisch T, Levin D, Zhao M, Santos S, Liu S, Cheng J, Lin FAuthor
Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Cell MovementCytokines
Humans
Skin
Sphingosine
T-Lymphocytes
Transendothelial and Transepithelial Migration
