title: The human cytokine TSLP triggers a cell-autonomous dendritic cell migration in confined environments.
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.
authors.affiliation: Inserm U932, Paris, France.
authors.forename: Maria-Isabel
authors.initials: MI
authors.lastname: Fernandez
authors.forename: Mélina L
authors.initials: ML
authors.lastname: Heuzé
authors.forename: Carolina
authors.initials: C
authors.lastname: Martinez-Cingolani
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Volpe
authors.forename: Marie-Helene
authors.initials: MH
authors.lastname: Donnadieu
authors.forename: Matthieu
authors.initials: M
authors.lastname: Piel
authors.forename: Bernhard
authors.initials: B
authors.lastname: Homey
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Lennon-Duménil
authors.forename: Vassili
authors.initials: V
authors.lastname: Soumelis
mesh_terms: D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D003599:Cytoskeleton / Q000276:immunology / Q000648:ultrastructure; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D046210:Microfluidic Analytical Techniques; D024462:Myosin Type II / Q000276:immunology / Q000648:ultrastructure; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D024462:Myosin Type II; D000094632:Thymic Stromal Lymphopoietin