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

ALVAREZ C; AMARAL, MARÍA MARTA; LANGELLOTTI, CECILIA; M VERMEULEN

IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2011 vol. 134 p. 185 - 197

0019-2805

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.