Investigations on T cell transmigration in a human skin-on-chip (SoC) model

Xiaoou Ren, Anthony E. Getschman, Samuel T Hwang, Brian F. Volkman, Thomas Klonisch, David Levin, Min Zhao, Susy Santos, Song Liu, Jasmine Cheng, Francis Lin

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1527-1539
Number of pages13
JournalLab on a Chip
Volume21
Issue number8
DOIs
StatePublished - Apr 21 2021

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Chemistry(all)
  • Biomedical Engineering

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