title: Glucocorticoids induce effector T cell depolarization via ERM proteins, thereby impeding migration and APC conjugation.
abstract: Glucocorticoids (GCs) repress lymphocyte function by controlling gene expression. In this study, we investigated Ag-specific effector T cells and provide evidence that GCs also modulate these cells' cytoskeletal architecture by nongenomic mechanisms. Following GC treatment, effector T cells rapidly lose their polarized morphology, which impedes both their migratory capacity and their interaction with APCs. The cytoskeleton rearrangements are preceded by an activation of ezrin-radixin-moesin proteins, which transiently increases the cellular rigidity but seems to occur independently of altered tyrosine phosphorylation. Phospholipase C activity is critically involved in mediating these nongenomic effects, because its inhibition prevents both T cell depolarization and ezrin-radixin-moesin phosphorylation after GC exposure. GC administration in vivo induced similar morphological changes in effector T cells as observed in vitro, suggesting that the above process plays a role in modulating inflammatory diseases. Taken together, our findings identify a novel mechanism through which GCs rapidly repress T cell function independently of gene transcription.
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, 97078 Würzburg, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Müller
authors.forename: Henrike J
authors.initials: HJ
authors.lastname: Fischer
authors.forename: Denise
authors.initials: D
authors.lastname: Tischner
authors.forename: Jens
authors.initials: J
authors.lastname: van den Brandt
authors.forename: Holger M
authors.initials: HM
authors.lastname: Reichardt
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D002464:Cell Migration Inhibition / Q000187:drug effects / Q000276:immunology*; D016764:Cell Polarity / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology*; D008565:Membrane Proteins / Q000502:physiology*; D008840:Microfilament Proteins / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D055647:Rats, Transgenic; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology* / Q000648:ultrastructure; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D003907:Dexamethasone; D008565:Membrane Proteins; D008840:Microfilament Proteins; D000099149:Ezrin; C071058:moesin; C071776:radixin