Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1095-102 |
| Number of pages | 8 |
| Journal | Blood |
| Volume | 109 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 1 Feb 2007 |
Keywords
- Animals
- Annexin A1
- Antigens, CD
- Antigens, Differentiation, T-Lymphocyte
- Arthritis
- Cell Differentiation
- Cell Proliferation
- Cells, Cultured
- Humans
- Immunity
- Interleukin-2 Receptor alpha Subunit
- Lectins, C-Type
- Lymphocyte Activation
- Mice
- Receptors, Antigen, T-Cell
- T-Lymphocytes
- Th1 Cells
- Journal Article
- Research Support, Non-U.S. Gov't