Source:http://linkedlifedata.com/resource/pubmed/id/21248258
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2011-2-3
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| pubmed:abstractText |
CD4 Th cells producing the proinflammatory cytokine IL-17 (Th17) have been implicated in a number of inflammatory arthritides including the spondyloarthritides. Th17 development is promoted by IL-23. Ankylosing spondylitis, the most common spondyloarthritis (SpA), is genetically associated with both HLA-B27 (B27) and IL-23R polymorphisms; however, the link remains unexplained. We have previously shown that B27 can form H chain dimers (termed B27(2)), which, unlike classical HLA-B27, bind the killer-cell Ig-like receptor KIR3DL2. In this article, we show that B27(2)-expressing APCs stimulate the survival, proliferation, and IL-17 production of KIR3DL2(+) CD4 T cells. KIR3DL2(+) CD4 T cells are expanded and enriched for IL-17 production in the blood and synovial fluid of patients with SpA. Despite KIR3DL2(+) cells comprising a mean of just 15% of CD4 T in the peripheral blood of SpA patients, this subset accounted for 70% of the observed increase in Th17 numbers in SpA patients compared with control subjects. TCR-stimulated peripheral blood KIR3DL2(+) CD4 T cell lines from SpA patients secreted 4-fold more IL-17 than KIR3DL2(+) lines from controls or KIR3DL2(-) CD4 T cells. Strikingly, KIR3DL2(+) CD4 T cells account for the majority of peripheral blood CD4 T cell IL-23R expression and produce more IL-17 in the presence of IL-23. Our findings link HLA-B27 with IL-17 production and suggest new therapeutic strategies in ankylosing spondylitis/SpA.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/HLA-B27 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/IL23R protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-17,
http://linkedlifedata.com/resource/pubmed/chemical/KIR3DL2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, KIR3DL2,
http://linkedlifedata.com/resource/pubmed/chemical/Superantigens
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| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
|
| pubmed:issn |
1550-6606
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
15
|
| pubmed:volume |
186
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2672-80
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| pubmed:dateRevised |
2011-11-11
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| pubmed:meshHeading |
pubmed-meshheading:21248258-Antigen-Presenting Cells,
pubmed-meshheading:21248258-CD4 Lymphocyte Count,
pubmed-meshheading:21248258-CD4-Positive T-Lymphocytes,
pubmed-meshheading:21248258-Cell Line,
pubmed-meshheading:21248258-Cell Proliferation,
pubmed-meshheading:21248258-Cell Survival,
pubmed-meshheading:21248258-Coculture Techniques,
pubmed-meshheading:21248258-Female,
pubmed-meshheading:21248258-HLA-B27 Antigen,
pubmed-meshheading:21248258-Humans,
pubmed-meshheading:21248258-Interleukin-17,
pubmed-meshheading:21248258-Lymphocyte Activation,
pubmed-meshheading:21248258-Male,
pubmed-meshheading:21248258-Protein Multimerization,
pubmed-meshheading:21248258-Receptors, Interleukin,
pubmed-meshheading:21248258-Receptors, KIR3DL2,
pubmed-meshheading:21248258-Spondylitis, Ankylosing,
pubmed-meshheading:21248258-Superantigens,
pubmed-meshheading:21248258-Th17 Cells
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| pubmed:year |
2011
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| pubmed:articleTitle |
Th17 cells expressing KIR3DL2+ and responsive to HLA-B27 homodimers are increased in ankylosing spondylitis.
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| pubmed:affiliation |
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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