Dexamethasone inhibits dendritic cell maturation by redirecting differentiation of a subset of cells

Richard Matasić, Allan B. Dietz, Stanimir Vuk-Pavlović

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

To investigate how corticosteroids affect differentiation of human dendritic cells (DC) in a defined inflammatory environment, we incubated immature DC with dexamethasone in the presence of tumor necrosis factor α (TNF-α), interleukin-1 (IL-1β), and prostaglandin E2. Dexamethasone inhibited differentiation into mature DC, as indicated by the reduced expression of antigen-presenting molecules, costimulatory and adhesion molecules, a marker of mature DC, and IL-12. Dexamethasone increased expression of CD14, CD36, and CD68, molecules characteristic of monocytes/macrophages and induced CD14+CD83- cells, a subset distinct both from immature DC and mature DC. The effects were concentration-dependent, with ID50 values between 2 and 30 nM dexamethasone. Unlike T and B cells, in DC dexamethasone induced no apoptosis, although it suppressed activated nuclear transcription factor NF-κB. Dexamethasone reduced the ability of DC to stimulate proliferation of allogeneic T cells in proportion to the level of CD14+CD83- cells in the population. CD83+ cells, isolated from dexamethasone-treated populations, retained the synthesis of IL-12 and the ability to stimulate proliferation of allogeneic T cells. Our data demonstrate that the dominant effect of the drug was redirecting differentiation of a subset of cells despite the presence of inflammatory cytokines. The observed ID50 values indicate that inhibition of DC differentiation might contribute significantly to in vivo immunosuppression by chronic administration of corticosteroids.

Original languageEnglish (US)
Pages (from-to)909-914
Number of pages6
JournalJournal of Leukocyte Biology
Volume66
Issue number6
DOIs
StatePublished - Dec 1999

Keywords

  • Cell surface molecules
  • Cellular differentiation
  • Immunomodulators

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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