Annexin-1-deficient dendritic cells acquire a mature phenotype during differentiation

Anthony Huggins, Nikolaos Paschalidis, Roderick J Flower, Mauro Perretti, Fulvio D'Acquisto

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Dendritic cells play a key role in the adaptive immune system by influencing T-cell differentiation. Annexin-1 (Anx-A1) has recently been shown to modulate the adaptive immune response by regulating T-cell activation and differentiation. Here we investigated the role of endogenous Anx-A1 in dendritic cells as major cellular counterpart of T-cell-driven immune response. We found that Anx-A1(-/-) bone marrow-derived dendritic cells show an increased number of CD11c(+) cells expressing high levels of some maturation markers, such as CD40, CD54, and CD80, coupled to a decreased capacity to take up antigen compared to control Anx-A1(+/+) cells. However, analysis of LPS-treated dendritic cells from Anx-A1(-/-) mice demonstrated a diminished up-regulation of maturation markers, a decreased migratory activity in vivo, and an attenuated production of the inflammatory cytokines interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-12. This defect was also accompanied by impaired nuclear factor (NF)-kappaB/DNA-binding activity and lack of Anx-A1 signaling, as demonstrated by the reduced activation of extracellular-signal regulated kinase (ERK)1/2 and Akt compared to cells from control littermates. As a consequence of this phenotype, Anx-A1(-/-) dendritic cells showed an impaired capacity to stimulate T-cell proliferation and differentiation in mixed leukocyte reaction. Together, these findings suggest that inhibition of Anx-A1 expression or function in dendritic cells might represent a useful way to modulate the adaptive immune response and pathogen-induced T-cell-driven immune diseases.

Original languageEnglish
Pages (from-to)985-96
Number of pages12
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Issue number4
Publication statusPublished - Apr 2009


  • Animals
  • Annexin A1
  • Antigen-Presenting Cells
  • B7-1 Antigen
  • Biomarkers
  • Bone Marrow Cells
  • CD11c Antigen
  • CD40 Antigens
  • Cell Differentiation
  • Cell Movement
  • Cells, Cultured
  • Cytokines
  • Dendritic Cells
  • Dextrans
  • Fluorescein-5-isothiocyanate
  • Fluorescent Dyes
  • Lipopolysaccharides
  • Lymphocyte Culture Test, Mixed
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • T-Lymphocytes
  • Time Factors
  • Up-Regulation
  • Journal Article
  • Research Support, Non-U.S. Gov't

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