Leukotriene C(4) prevents the complete maturation of murine dendritic cells and modifies interleukin-12/interleukin-23 balance

Immunology. 2011 Oct;134(2):185-97. doi: 10.1111/j.1365-2567.2011.03478.x.

Abstract

Leukotriene C(4) is an important mediator in the development of inflammatory reactions and ischaemia. Previous studies have shown that leukotriene C(4) is able to modulate the function of dendritic cells (DCs) and induce their chemotaxis from skin to lymph node. In this study, we decided to evaluate the modulation exerted by leukotriene C(4) on DCs, depending on their status of activation. We showed for the first time that leukotriene C(4) stimulates endocytosis both in immature and lipopolysaccharide (LPS) -activated DCs. Moreover, it suppressed the interleukin-12p70 (IL-12p70) release, but induces the secretion of IL-23 by DCs activated with LPS and promotes the expansion of T helper type 17 (Th17) lymphocytes. Furthermore, blocking the release of IL-23 reduced the percentages of CD4(+) T cells producing IL-17 in a mixed lymphocyte reaction. Ours results suggest that leukotriene C(4) interferes with the complete maturation of inflammatory DCs in terms of phenotype and antigen uptake, while favouring the release of IL-23, the main cytokine involved in the maintenance of the Th17 profile.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Endocytosis / immunology
  • Female
  • Interleukin-12 / immunology*
  • Interleukin-23 / immunology*
  • Leukotriene C4 / immunology*
  • Lipopolysaccharides / immunology
  • Mice
  • Mice, Inbred C57BL
  • Th17 Cells / immunology

Substances

  • Interleukin-23
  • Lipopolysaccharides
  • Interleukin-12
  • Leukotriene C4