@Article{ecn.2007.0089,
AUTHOR = {Lorena Salazar, Octavio Aravena, Juan Contreras-Levicoy, Barbara Pesce, Diego Catalan, Roberto Zuniga, Mirentxu Iruretagoyena, Alexis M. Kalergis, Juan C. Aguillón},
TITLE = {Short-term lipopolysaccharide stimulation induces differentiation of murine bone marrow-derived dendritic cells into a tolerogenic phenotype},
JOURNAL = {European Cytokine Network},
VOLUME = {18},
YEAR = {2007},
NUMBER = {2},
PAGES = {78--85},
URL = {http://www.techscience.com/ECN/v18n2/65999},
ISSN = {1952-4005},
ABSTRACT = {Dendritic cells (DCs) are professional, antigen-presenting cells, which induce and regulate T cell
reactivity. DCs are crucial in innate and adaptive immune responses, and are also involved in central and
peripheral tolerance induction. Tolerance can be mediated by immature and semi-mature DCs expressing low
levels of co-stimulator and major histocompatibility complex (MHC) molecules. The aim of this study was to
investigate the ability of short-term lipopolysaccharide (LPS) stimulation to modulate the stage of differentiation
of bone marrow-derived DCs. For this purpose, DCs obtained from DBA1/lacJ mice were stimulated for four
(4hLPS/DCs) or 24 (24hLPS/DCs) hours with LPS, using DCs without stimulation (0hLPS/DCs) as a control. Flow
cytometry analysis of 4hLPS/DCs showed intermediate CD40 and MHC class II expression, lower than that of
24hLPS/DCs (fully mature), and greater than that of 0hLPS/DCs (immature). A functional assay showed that
4hLPS/DCs displayed increased endocytotic ability compared to 24hLPS/DCs, indicating a semi-mature state.
4hLPS/DCs were greater producers of IL-10 protein and TGFb1 mRNA than 24hLPS/DCs and immature DCs,
displaying a cytokine production pattern that is characteristic of tolerogenic DCs. An assay for antigen-presenting
capacity demonstrated that 4hLPS/DCs induced secretion of IL-2 from an OTH4 T cell hybridoma, indicating a
functional presenting activity. Finally, the tolerogenic phenotype of 4hLPS/DCs was demonstrated by their ability
to interfere with the progression of bovine type II collagen (bII)-induced arthritis (CIA) when they were loaded
with bCII antigen and injected into mice with established CIA. We conclude that the stimulation of murine bone
marrow-derived DCs with LPS for four hours generates semi-mature DCs with tolerogenic capability.},
DOI = {10.1684/ecn.2007.0089}
}