Lipoxin-mediated inhibition of IL-12 production by DCs: a mechanism for regulation of microbial immunity
Lipoxin-mediated inhibition of IL-12 production by DCs: a mechanism for regulation of microbial immunity
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DOI：
10.1038/ni745
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发表时间：
2002-01-01
影响因子：
30.5
通讯作者：
Sher, A
中科院分区：
文献类型：
--
作者：
Aliberti, J;Hieny, S;Sher, A
脂氧素是类二十烷酸介质，对急性炎症过程具有有效的抑制作用。我们在此表明，在用弓形虫提取物进行微生物刺激后，脂氧素 A(4) (LXA(4)) 的诱导伴随着小鼠脾树突状细胞 (DC) 体内白细胞介素 12 (IL-12) 反应性的抑制。在缺乏参与 LXA4 生物合成的关键脂氧合酶的小鼠中，无法触发 DC 功能的麻痹。此外，用LXA4预处理的DC在体外对微生物刺激产生IL-12产生抵抗，并且注射稳定的LXA(4)类似物的小鼠在体内表现出脾DC动员和IL-12反应减少。总之，这些发现表明，响应微生物刺激而诱导脂氧素可以为在对病原体的先天反应过程中调节 DC 功能提供有效的机制。
Lipoxins are eicosanoid mediators that show potent inhibitory effects on the acute inflammatory process. We show here that the induction of lipoxin A(4) (LXA(4)) accompanied the In vivo suppression of interleukin 12 (IL-12) responsiveness of murine splenic dendritic cells (DCs) after microbial stimulation with an extract of Toxoplasma gondii. This paralysis of DC function could not be triggered in mice that were deficient in a key lipoxygenase involved in LXA4 biosynthesis. In addition, DCs pre-treated with LXA4 became refractory to microbial stimulation for IL-12 production In vitro and mice injected with a stable LXA(4) analog showed reduced splenic DC mobilization and IL-12 responses in vivo. Together, these findings indicate that the induction of lipoxins in response to microbial stimulation can provide a potent mechanism for regulating DC function during the innate response to pathogens.