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Rheumatology Advance Access originally published online on April 4, 2008
Rheumatology 2008 47(5):636-639; doi:10.1093/rheumatology/ken062
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Glucocorticoid treatment inhibits annexin-1 expression in rheumatoid arthritis CD4+ T cells

F. D'Acquisto1, N. Paschalidis1, K. Raza2, C. D. Buckley2, R. J. Flower1 and M. Perretti1

1William Harvey Research Institute, Barts and The London, Charterhouse Square, London and 2Division of Immunity and Infection, MRC Centre for Immune Regulation, University of Birmingham, Edgbaston, UK.

Correspondence to: F. D'Acquisto, The William Harvey Research Institute, Centre for Biochemical Pharmacology, Barts and The London, Queen Mary School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK. E-mail: F.Dacquisto{at}qmul.ac.uk


  Abstract

Objective. Annexin-1 (Anx-A1) has been recently shown to play a key role in T-cell activation and to be highly expressed in T cells from RA patients. Here, we investigated the effects of glucocorticoids (GCs) on Anx-A1 expression in T cells in vitro and in vivo.

Methods. To evaluate the effects of dexamethasone (Dex) on Anx-A1 expression, human peripheral blood T cells were incubated with Dex and then analysed by real-time PCR and western blotting. Similar experiments were carried out in vivo by measuring Anx-A1 levels in T cells from patients with RA before and after administration of steroids.

Results. Incubation of T cells with Dex decreased Anx-A1 levels in a time-dependent fashion and almost abolished its expression after 12 h. Stimulation of T cells pre-incubated with Dex for 12 h with anti-CD3/CD28 led to significant reduction of IL-2 production. Addition of human recombinant Anx-A1 to Dex-treated cells reversed the inhibitory effects of the steroids on anti-CD3/CD28-induced IL-2 production. Treatment of RA patients with steroid decreased Anx-A1 expression in T cells.

Conclusions. GCs suppress Anx-A1 expression in T cells in vitro and in vivo. These results provide evidence for a novel pathway by which steroids regulate the adaptive immune response and suggest that Anx-A1 may represent a target for the treatment of autoimmune diseases.

KEY WORDS: Annnexin-1, Glucocorticoids, T cells, RA

Submitted 5 September 2007; revised version accepted 28 January 2008.
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