Glucocorticoids induce effector T cell depolarization via ERM proteins, thereby impeding migration and APC conjugation.

نویسندگان

  • Nora Müller
  • Henrike J Fischer
  • Denise Tischner
  • Jens van den Brandt
  • Holger M Reichardt
چکیده

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.

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عنوان ژورنال:
  • Journal of immunology

دوره 190 8  شماره 

صفحات  -

تاریخ انتشار 2013