期刊
BLOOD
卷 109, 期 3, 页码 1095-1102出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2006-05-022798
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资金
- Medical Research Council [G116/131, G0400327, G9818340B] Funding Source: researchfish
- Medical Research Council [G116/131, G0400327] Funding Source: Medline
- Wellcome Trust [040269, 069 234/Z/02/Z, 040 269/Z/96/A] Funding Source: Medline
- MRC [G116/131, G0400327] Funding Source: UKRI
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.
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