| First Author | D'Acquisto F | Year | 2007 |
| Journal | Blood | Volume | 109 |
| Issue | 3 | Pages | 1095-102 |
| PubMed ID | 17008549 | Mgi Jnum | J:144395 |
| Mgi Id | MGI:3830887 | Doi | 10.1182/blood-2006-05-022798 |
| Citation | D'Acquisto F, et al. (2007) Annexin-1 modulates T-cell activation and differentiation. Blood 109(3):1095-102 |
| abstractText | 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-kappaB (NF-kappaB), 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 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 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. |
