Immunology Laboratory, Institute of Haematologic Research, National Academy of Medicine, Buenos Aires, Argentina.
Immunology. 2011 Oct;134(2):185-97. doi: 10.1111/j.1365-2567.2011.03478.x.
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.
白三烯 C(4) 是炎症反应和缺血的重要介质。先前的研究表明,白三烯 C(4) 能够调节树突状细胞 (DC) 的功能,并诱导其从皮肤向淋巴结趋化。在这项研究中,我们决定评估白三烯 C(4)对处于不同激活状态的 DC 所产生的调节作用。我们首次表明,白三烯 C(4) 刺激未成熟和脂多糖 (LPS) 激活的 DC 的内吞作用。此外,它抑制白细胞介素-12p70 (IL-12p70) 的释放,但诱导 LPS 激活的 DC 分泌 IL-23,并促进辅助性 T 细胞 17 (Th17) 淋巴细胞的扩增。此外,阻断 IL-23 的释放会降低混合淋巴细胞反应中产生 IL-17 的 CD4(+) T 细胞的百分比。我们的结果表明,白三烯 C(4) 干扰炎症性 DC 从表型和抗原摄取方面的完全成熟,同时有利于 IL-23 的释放,IL-23 是维持 Th17 表型的主要细胞因子。