Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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A more recent version of this article appeared on July 1, 2007

Published online before print April 30, 2007
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0406267


Received for publication April 12, 2006.
Revised March 13, 2007.
Accepted for publication March 14, 2007.


Article

LPS induces rapid IL-10 release by M-CSF-conditioned, tolerogenic dendritic cell precursors

Wing-Hong Kwan @, Charlotte Boix , Nicolas Gougelet , Wolf H. Fridman , and Chris G. F. Mueller

INSERM UMRS 872, Université Pierre et Marie Curie-Paris 6, Université René Descartes-Paris 5, Centre de Recherches Biomédicales des Cordeliers, Paris, France

@ To whom correspondence should be addressed. E-mail: wing-hong.kwan{at}u255.bhdc.jussieu.fr.


   Abstract

Dendritic cells (DC) obtained by culturing myeloid precursors in GM-CSF undergo maturation and induce an efficient T cell response when stimulated with microbial products. DC precursors themselves also recognize microbial products, and it remains unclear how these stimulated DC precursors modulate the immune response. We show here that M-CSF-conditioned human DC precursors respond to LPS, Mycobacteria bovis, and inflammatory cytokines by a rapid and robust production of IL-10, largely superior to that observed with immature DC or monocytes. The endogenous IL-10 restrained the DC precursors from converting into professional APC, as blocking the IL-10 receptor in the presence of LPS resulted in the formation of efficient T cell stimulators. LPS stimulation concomitant with DC differentiation gave rise to immature DC, which were tolerant to a secondary LPS exposure. Furthermore, the LPS-activated DC precursors reduced bystander DC maturation and anti-CD3/CD28-triggered T cell activation. These data suggest that when exposed to inflammatory or microbial signals, M-CSF-conditioned DC precursors can participate in the modulation of inflammation and immune response by rapid release of IL-10.

Key Words: growth factor • cytokine • differentiation • activation • tolerance




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