Dexamethasone induces IL-10-producing monocyte-derived dendritic cells with durable immaturity

Scand J Immunol. 2005 Jul;62(1):45-54. doi: 10.1111/j.1365-3083.2005.01640.x.


It is highly desirable that immature dendritic cells (DC) used for tolerance induction maintain steady immature state with predominant interleukin (IL)-10 production. In this study, we attempted to develop DC with durable immaturity and other tolerogenic features by using dexamethasone (Dex). We found DC derived from human monocytes in the presence of 10(-7) m Dex were negative for CD1a. Compared with control transduced DC (Ctrl-DC), Dex-DC expressed lower CD40, CD80 and CD86 but equivalent human leucocyte antigen-DR. Both immature Dex- and Ctrl-DC did not express CD83. Nevertheless, upon stimulation of lipopolysaccharide (LPS) or CD40 ligand, the expression of CD40, CD80, CD83 and CD86 was upregulated on Ctrl-DC but not on Dex-DC. The immaturity of Dex-DC was durable following Dex removal. Interestingly, Dex-DC maintained production of large amount of IL-10 and little IL-12 five days after Dex removed. Further study indicated that high-level IL-10 production by Dex-DC was associated with high-level phosphorylation of extracellular signal-regulated kinase (ERK) as blockade of this enzyme markedly attenuated IL-10 production. Furthermore, Dex-DC sustained the capability of high phosphorylation of ERK and IL-10 production 5 days after Dex removal. In addition, Dex-DC had significantly lower activity in stimulating T-cell proliferation. Neutralization of IL-10, to some extent, promoted DC maturation activated by LPS, as well as T-cell stimulatory activity of Dex-DC. The above findings suggest that IL-10-producing Dex-DC with durable immaturity are potentially useful for induction of immune tolerance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Antigens, CD1 / analysis
  • Cell Differentiation
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dexamethasone / pharmacology*
  • Endocytosis
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Immune Tolerance*
  • Interleukin-10 / metabolism*
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation
  • Monocytes / drug effects
  • Phosphorylation
  • T-Lymphocytes / immunology


  • Antigens, CD
  • Antigens, CD1
  • CD1a antigen
  • Lipopolysaccharides
  • Interleukin-10
  • Dexamethasone
  • Extracellular Signal-Regulated MAP Kinases