Dexamethasone induces IL-10-producing monocyte-derived dendritic cells with durable immaturity.
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.
Xia
C-Q
CQ
Department of Pathology, Immunology, Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.
Peng
R
R
Beato
F
F
Clare-Salzler
M J
MJ
D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D018949:Antigens, CD1 / Q000032:analysis; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology*; D004705:Endocytosis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000187:drug effects; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D018949:Antigens, CD1; C419393:CD1a antigen; D008070:Lipopolysaccharides; D016753:Interleukin-10; D003907:Dexamethasone; D048049:Extracellular Signal-Regulated MAP Kinases