Increased circulating CD11b+CD11c+ dendritic cells (DC) in aged BWF1 mice which can be matured by TNF-alpha into BLC/CXCL13-producing DC

Eur J Immunol. 2002 Jul;32(7):1881-7. doi: 10.1002/1521-4141(200207)32:7<1881::AID-IMMU1881>3.0.CO;2-Z.

Abstract

Dendritic cells (DC) play a pivotal role in regulating immune responses. We previously reported aberrant high production of B lymphocyte chemoattractant (BLC/CXCL13) by DC in aged BWF1 mice, amurine model for systemic lupus erythematosus (SLE). We describe here that CD11b+CD11c+ cells were markedly increased in the peripheral blood (PBL-DC) in aged BWF1, but not in similarly aged NZB or NZW mice. Part of PBL-DC showed a typical dendritic morphology and expressed MHC class II molecules, and had a weak, but significant antigen-presenting ability in mixed lymphocytereaction. PBL-DC were chemoattracted to several chemokines in vitro including secondary lymphoid tissue chemokine (SLC), liver and activation-regulated chemokine (LARC), RANTES, macrophage inflammatory protein-1alpha, whereas splenic mature DC from aged BWF1 mice were preferentially chemoattracted towards SLC. BLC production was induced when PBL-DC were cultured in the presence of TNF-alpha for 3 days. BLC expression was also induced in bone marrow-derived DC when they were differentiated into mature DC in the presence of TNF-alpha and IL-1beta, while both IFN-alpha and IFN-gamma failed to induce BLC expression in bone marrow-derived DC. Since TNF-alpha expression is increased in aged BWF1 mice, DC recruitment in the circulation and maturation into BLC-producing DC by TNF-alpha may play a pivotal role in the development of systemic autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology*
  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • Biomarkers
  • Cell Differentiation
  • Cells, Cultured
  • Chemokine CXCL13
  • Chemokines, CXC / biosynthesis*
  • Chemotaxis, Leukocyte / immunology
  • Dendritic Cells / cytology*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Disease Models, Animal
  • Gene Expression / drug effects
  • Integrin alphaXbeta2 / immunology*
  • Interferon-alpha / pharmacology
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Leukocyte Count
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / immunology*
  • Macrophage-1 Antigen / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Rats
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Biomarkers
  • Chemokine CXCL13
  • Chemokines, CXC
  • Cxcl13 protein, mouse
  • Integrin alphaXbeta2
  • Interferon-alpha
  • Interleukin-1
  • Macrophage-1 Antigen
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma