脂氧素介导的树突状细胞对白细胞介素-12产生的抑制作用：一种调节微生物免疫的机制

Lipoxin-mediated inhibition of IL-12 production by DCs: a mechanism for regulation of microbial immunity.

作者信息

Aliberti J, Hieny S, Reis e Sousa C, Serhan C N, Sher A

机构信息

Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

出版信息

Nat Immunol. 2002 Jan;3(1):76-82. doi: 10.1038/ni745. Epub 2001 Dec 17.

DOI:10.1038/ni745

PMID:11743584

Abstract

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 LXA(4) biosynthesis. In addition, DCs pre-treated with LXA(4) 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.

摘要

脂氧素是一类类花生酸介质，对急性炎症过程具有强大的抑制作用。我们在此表明，在用刚地弓形虫提取物进行微生物刺激后，脂氧素A4（LXA4）的诱导伴随着小鼠脾脏树突状细胞（DCs）白细胞介素12（IL-12）反应性的体内抑制。在参与LXA4生物合成的关键脂氧合酶缺陷的小鼠中，这种DC功能的麻痹无法被触发。此外，用LXA4预处理的DCs在体外对微生物刺激产生IL-12变得不敏感，并且注射稳定LXA4类似物的小鼠在体内脾脏DC动员和IL-12反应降低。总之，这些发现表明，响应微生物刺激而诱导脂氧素可提供一种在对病原体的先天反应期间调节DC功能的强大机制。