Annexin-1 modulates T-cell activation and differentiation

F D'Aqcquisto, A Merghani, E Lecona, G Rosignoli, Karim Raza, Christopher Buckley, RJ Flower, M Perretti

Research output: Contribution to journalArticlepeer-review

103 Citations (Scopus)
12 Downloads (Pure)


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 have never been explored. Although 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 nuclear factor-kappa B (NF-kappa B), nuclear factor of activated T cells (NFATs), and activator protein-1 (AP-1) activation and preceded by a rapid T-cell receptor (TCR)-induced externalization of the annexin-1 receptor. Interestingly, differentiation of naive T cells in the presence of annexin-1 increased skewing in Th1 cells; in the collageninduced 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 up-regulation 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 etiologic factor.
Original languageEnglish
Pages (from-to)1095-1102
Number of pages8
Issue number3
Publication statusPublished - 5 Oct 2006


Dive into the research topics of 'Annexin-1 modulates T-cell activation and differentiation'. Together they form a unique fingerprint.

Cite this