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Blood, 1 February 2007, Vol. 109, No. 3, pp. 1095-1102.
Prepublished online as a Blood First Edition Paper on September 28, 2006; DOI 10.1182/blood-2006-05-022798.
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Submitted May 11, 2006
Accepted September 8, 2006
Annexin 1 modulates T cell activation and differentiation
Fulvio D'Acquisto*, Ahmed Merghani, Emilio Lecona, Guglielmo Rosignoli, Karim Raza, Christopher D Buckley, Roderick J Flower, and Mauro Perretti
The William Harvey Research Institute, Centre for Biochemical Pharmacology, London, UK
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK
* Corresponding author; email: f.dacquisto{at}qmul.ac.uk.
Annexin-1 is an anti-inflammatory protein that plays an important homeostatic role in innate immunity, however its potential actions in the modulation of adaptive immunity has never been explored. Whilst inactive by itself, addition of annexin-1 to stimulated T cells augmented anti-CD3/CD28-mediated CD25 and CD69 expression and cell proliferation. This effect was paralleled by increased NF- B, AP-1 and NFAT activation and preceded by a rapid TCR-induced externalization of the annexin-1 receptor. Interestingly, differentiation of naive T cells in presence of annexin-1 increased skewing in Th1 cells; in the collagen induced arthritis model treatment of mice with annexin-1 during the immunization phase exacerbated signs and symptoms at disease onset. Consistent with these findings blood CD4+ cells from patients with rheumatoid arthritis showed a marked upregulation of annexin-1 expression. Together these results demonstrate that Annexin-1 is a molecular "tuner" of TCR signaling and suggest this protein might represent a new target for the development of drugs directed to pathologies where an unbalanced Th1/Th2 response or an aberrant activation of T cells is the major etiological factor.
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