Investigations on T cell transmigration in a human skin-on-chip (SoC) model
- 22 February 2021
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Lab on a Chip
- Vol. 21 (8), 1527-1539
- https://doi.org/10.1039/d0lc01194k
Abstract
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.Keywords
Funding Information
- Natural Sciences and Engineering Research Council of Canada (RGPIN-2014-04789)
- University of Manitoba
- National Psoriasis Foundation
- Defense Advanced Research Projects Agency (D20AC00003)
- Air Force Office of Scientific Research (FA9550-16-1-0052)
- Multidisciplinary University Research Initiative (FA9550-16-1-0052)
- National Institutes of Health (R01EY019101)
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