Increased and long-term generation of dendritic cells with reduced function from IL-6-deficient bone marrow Journal Article

Authors: Bleier, J. I.; Pillarisetty, V. G.; Shah, A. B.; DeMatteo, R. P.
Article Title: Increased and long-term generation of dendritic cells with reduced function from IL-6-deficient bone marrow
Abstract: The importance of IL-6 in dendritic cell (DC) development and function has not been well defined. To establish the role of IL-6, we studied bone marrow-derived DC (BMDC) and freshly isolated splenic DC from IL-6 -/--transgenic mice. We found that although IL-6-/- bone marrow had a similar composition to that of wild-type (WT) mice, it generated up to 10 times more DC when cultured in GM-CSF. The difference persisted even when IL-6-/- and WT bone marrow were cultured together, excluding the possibility that the effects were simply due to different cytokine microenvironments. In comparison to WT BMDC, IL-6-/- BMDC captured at least as much Ag, had an equivalent surface phenotype, and matured similarly in response to LPS or CpG. However, IL-6-/-BMDC induced less T cell allostimulation and Ag-specific T cell activation, but only the former was related to their inability to generate IL-6. Although WT bone marrow cultures died within 4 wk, IL-6-/- cultures continued to generate BMDC for > 120 days, although the BMDC became immature and less functional. In vivo, we found that IL-6-/- mice had similar numbers and types of splenic DC as WT mice, both normally and after treatment with either Flt-3 ligand or GM-CSF. These findings demonstrate that IL-6 has profound effects on DC development in vitro, although the number and subtype composition of DC are unaffected by the absence of IL-6 in vivo. Furthermore, secretion of IL-6 is critical to certain DC functions.
Keywords: nonhuman; flow cytometry; animal cell; mouse; animals; mice; mice, knockout; bone marrow cells; cells, cultured; cell division; bone marrow; spleen; dendritic cell; enzyme linked immunosorbent assay; mice, inbred strains; antigen presentation; lymphocyte activation; cytokines; dendritic cells; cellular immunity; tumor necrosis factor alpha; interleukin 6; interleukin-6; lipopolysaccharide; immunophenotyping; virus recombinant; spleen cell; adenovirus; granulocyte-macrophage colony-stimulating factor; male; priority journal; article
Journal Title: Journal of Immunology
Volume: 172
Issue: 12
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 2004-06-15
Start Page: 7408
End Page: 7416
Language: English
PROVIDER: scopus
PUBMED: 15187118
DOI: 10.4049/​jimmunol.172.12.7408
Notes: J. Immunol. -- Cited By (since 1996):21 -- Export Date: 16 June 2014 -- CODEN: JOIMA C2 - 15187118 -- Source: Scopus
Citation Impact
MSK Authors
  1. Ronald P DeMatteo
    635 DeMatteo
  2. Joshua Israel Bleier
    13 Bleier
  3. Alaap Shah
    20 Shah