Leukotriene C4 prevents the complete maturation of murine dendritic cells and modifies interleukin-12/interleukin-23 balance.

Summary Leukotriene C₄ is an important mediator in the development of inflammatory reactions and ischaemia. Previous studies have shown that leukotriene C₄ 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 C₄ on DCs, depending on their status of activation. We showed for the first time that leukotriene C₄ 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 C₄ 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. [ABSTRACT FROM AUTHOR]