| Retinal cells suppress intraocular inflammation (uveitis) through production of interleukin-27 and interleukin-10. | |
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MedLine Citation:
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PMID: 21294722 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Neuronal or photoreceptor deficit observed in uveitis and multiple sclerosis derives in part from inability to control inflammatory responses in neuroretina or brain. Recently, IL-27 was found to play a role in suppressing experimental autoimmune uveitis and experimental autoimmune encephalomyelitis, two animal models that share essential pathological features of human uveitis and multiple sclerosis, respectively. However, the mechanism by which interleukin-27 (IL-27) inhibits central nervous system (CNS) inflammation is not clear. In this study we have investigated mechanisms that mitigate or curtail intraocular inflammation (uveitis) and examined whether inhibitory effects of IL-27 are mediated locally by neuroretinal cells or by regulatory T cells. We show here that microglia cells in the neuroretina constitutively secrete IL-27 and its expression is up-regulated during uveitis. We further show that photoreceptors constitutively express IL-27 receptor and respond to IL-27 signalling by producing anti-inflammatory molecules, IL-10 and suppressor of cytokine signalling 1 (SOCS1) through signal transducer and activator of transcription 1 (STAT1) -dependent mechanisms. Moreover, STAT1-deficient mice produced reduced amounts of IL-27, IL-10 and SOCS1 and developed more severe uveitis. Surprisingly, IL-10-producing regulatory T cells had marginal roles in suppressing uveitis. These results suggest that suppression of intraocular inflammation might be mediated through endogenous production of IL-27 and IL-10 by retinal cells, whereas SOCS proteins induced by IL-27 during uveitis may function to protect the neuroretinal cells from the toxic effects of pro-inflammatory cytokines. Targeted delivery of IL-27 into immune privileged tissues of the CNS may therefore be beneficial in the treatment of CNS inflammatory diseases, such as uveitis and multiple sclerosis. |
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Authors:
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Yun Sang Lee; Ahjoku Amadi-Obi; Cheng-Rong Yu; Charles E Egwuagu |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural Date: 2011-02-07 |
Journal Detail:
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Title: Immunology Volume: 132 ISSN: 1365-2567 ISO Abbreviation: Immunology Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-11 Completed Date: 2011-06-06 Revised Date: 2012-04-02 |
Medline Journal Info:
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Nlm Unique ID: 0374672 Medline TA: Immunology Country: England |
Other Details:
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Languages: eng Pagination: 492-502 Citation Subset: IM |
Copyright Information:
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© 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd. |
Affiliation:
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Molecular Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1857, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Animals Blotting, Western Cell Line Cells, Cultured Central Nervous System / immunology, metabolism, pathology Female Humans Interleukin-10 / genetics, immunology*, metabolism Interleukin-17 / genetics, immunology*, metabolism Mice Mice, Inbred C57BL Mice, Knockout Microglia / immunology, metabolism Microscopy, Confocal Receptors, Interleukin / genetics, immunology, metabolism Retina / immunology*, metabolism, pathology Reverse Transcriptase Polymerase Chain Reaction STAT1 Transcription Factor / genetics, immunology, metabolism Suppressor of Cytokine Signaling Proteins / genetics, immunology, metabolism T-Lymphocytes, Regulatory / immunology, metabolism Uveitis / genetics, immunology*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-17; 0/Receptors, Interleukin; 0/STAT1 Transcription Factor; 0/Socs1 protein, mouse; 0/Suppressor of Cytokine Signaling Proteins; 130068-27-8/Interleukin-10 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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