| Inflammation in the central nervous system and Th17 responses are inhibited by IFN-gamma-Induced IL-18 binding protein. | |
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MedLine Citation:
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PMID: 20644165 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Inflammatory responses are essential for immune protection but may also cause pathology and must be regulated. Both Th1 and Th17 cells are implicated in the pathogenesis of autoimmune inflammatory diseases, such as multiple sclerosis. We show in this study that IL-18-binding protein (IL-18bp), the endogenous inhibitor of the Th1-promoting cytokine IL-18, is upregulated by IFN-gamma in resident microglial cells in the CNS during multiple sclerosis-like disease in mice. Test of function by overexpression of IL-18bp in the CNS using a viral vector led to marked reduction in Th17 responses and robust inhibition of incidence, severity, and histopathology of disease, independently of IFN-gamma. The disease-limiting action of IL-18bp included suppression of APC-derived Th17-polarizing cytokines. IL-18bp thus acts as a sensor for IFN-gamma and can regulate both Th1 and Th17 responses in the CNS. |
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Authors:
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Jason M Millward; Morten Løbner; Rachel D Wheeler; Trevor Owens |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-19 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-05 Completed Date: 2010-09-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 2458-66 Citation Subset: AIM; IM |
Affiliation:
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Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Central Nervous System / drug effects, immunology*, pathology Encephalomyelitis, Autoimmune, Experimental / genetics, immunology, prevention & control Female Flow Cytometry Humans Inflammation / genetics, immunology*, prevention & control Injections, Spinal Intercellular Signaling Peptides and Proteins / administration & dosage, genetics, immunology* Interferon-gamma / genetics, immunology* Interleukin-17 / immunology, metabolism Interleukin-18 / genetics, immunology Male Mice Mice, Inbred C57BL Mice, Knockout Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes, Helper-Inducer / immunology*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Intercellular Signaling Peptides and Proteins; 0/Interleukin-17; 0/Interleukin-18; 0/interleukin-18 binding protein; 82115-62-6/Interferon-gamma |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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