The human cytokine TSLP triggers a cell-autonomous dendritic cell migration in confined environments

Maria Isabel Fernandez, Mélina L. Heuzé, Carolina Martinez-Cingolani, Elisabetta Volpe, Marie Helene Donnadieu, Matthieu Piel, Bernhard Homey, Ana Maria Lennon-Duménil, Vassili Soumelis

Research output: Contribution to journalArticlepeer-review

Abstract

Dendritic cells (DCs) need to migrate in the interstitial environment of peripheral tissues to reach secondary lymphoid organs and initiate a suitable immune response. Whether and how inflamed tissues instruct DCs to emigrate is not fully understood. In this study, we report the unexpected finding that the epithelial-derived cytokine TSLP triggers chemokinesis of resting primary human DCs in a cell-autonomous manner. TSLP induced the polarization of both microtubule and actin cytoskeletons and promoted DC 3-dimensional migration in transwell as well as in microfabricated channels that mimic the confined environment of peripheral tissues. TSLP-induced migration relied on the actin-based motor myosin II and was inhibited by blebbistatin. Accordingly, TSLP triggered the redistribution of phosphorylated myosin II regulatory light chain to the actin cortex, indicating that TSLP induces DC migration by promoting actomyosin contractility. Thus, TSLP produced by epithelial cells in inflamed tissue has a critical function in licensing DCs for cell-autonomous migration. This indicates that cytokines can directly trigger cell migration, which has important implications in immune physiopathology and vaccine design.

Original languageEnglish
Pages (from-to)3862-3869
Number of pages8
JournalBlood
Volume118
Issue number14
DOIs
Publication statusPublished - Oct 6 2011

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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