Nature Immunology
3, 76 - 82 (2001)
Published online: 17 December 2001; | doi:10.1038/ni745
Lipoxin-mediated inhibition of IL-12 production by DCs: a mechanism for regulation of microbial immunityJ. Aliberti1, S. Hieny1, C. Reis e Sousa2, C. N. Serhan3
& A. Sher11
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 2
Immunobiology Laboratory, Imperial Cancer Research Fund, London, UK. 3
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Correspondence should be addressed to J. Aliberti jaliberti@niaid.nih.govLipoxins are eicosanoid mediators that show potent inhibitory effects on the acute inflammatory process. We show here that the induction of lipoxin A4 (LXA4) 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 LXA4 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.
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