Annexin-1 modulates T-cell activation and differentiation

Blood. 2007 Feb 1;109(3):1095-102. doi: 10.1182/blood-2006-05-022798. Epub 2006 Sep 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A1 / physiology*
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Arthritis / drug therapy
  • Arthritis / etiology
  • Cell Differentiation*
  • Cell Proliferation
  • Cells, Cultured
  • Humans
  • Immunity
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type
  • Lymphocyte Activation*
  • Mice
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / cytology*
  • Th1 Cells

Substances

  • Annexin A1
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type
  • Receptors, Antigen, T-Cell