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http://purl.uniprot.org/citations/26841353http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26841353http://www.w3.org/2000/01/rdf-schema#comment"

Objective

In the spondyloarthritides (SpA), increased numbers of CD4+ T cells express killer cell immunoglobulin-like receptor 3DL2 (KIR-3DL2). The aim of this study was to determine the factors that induce KIR-3DL2 expression, and to characterize the relationship between HLA-B27 and the phenotype and function of KIR-3DL2-expressing CD4+ T cells in SpA.

Methods

In total, 34 B27+ patients with SpA, 28 age- and sex-matched healthy controls (20 B27- and 8 B27+), and 9 patients with rheumatoid arthritis were studied. KIR-3DL2 expression and other phenotypic characteristics of peripheral blood and synovial fluid CD4+ T cells were studied by flow cytometry, quantitative polymerase chain reaction, and Western blotting. T cell receptor clonality was determined by template-switch anchored reverse transcription-polymerase chain reaction and sequencing analysis. Cytokines were measured by enzyme-linked immunosorbent assay.

Results

Cellular activation induced KIR-3DL2 expression on both naive and effector CD4+ T cells. KIR-3DL2 binding to B27+ cells promoted expression of KIR-3DL2, the Th17-specific transcription factor retinoic acid receptor-related orphan nuclear receptor γt, and the antiapoptotic factor B cell lymphoma 2. KIR-3DL2+CD4+ T cells in patients with ankylosing spondylitis were oligoclonal and enriched for markers of T cell activation and for the gut homing receptor CCR9. In the presence of B27+ antigen-presenting cells, KIR-3DL2+CD4+ T cells produced less interleukin-2 (IL-2) but more IL-17. This effect was blocked by HC10, an antibody that inhibits the binding of KIR-3DL2 to B27 heavy chains.

Conclusion

KIR-3DL2 binding to HLA-B27 licenses Th17 cell differentiation in SpA. These findings raise the therapeutic potential of targeting HLA-B27-KIR-3DL2 interactions for the treatment of B27+ patients with SpA."xsd:string
http://purl.uniprot.org/citations/26841353http://purl.org/dc/terms/identifier"doi:10.1002/art.39515"xsd:string
http://purl.uniprot.org/citations/26841353http://purl.uniprot.org/core/author"Shaw J."xsd:string
http://purl.uniprot.org/citations/26841353http://purl.uniprot.org/core/author"Ridley A."xsd:string
http://purl.uniprot.org/citations/26841353http://purl.uniprot.org/core/author"Bowness P."xsd:string
http://purl.uniprot.org/citations/26841353http://purl.uniprot.org/core/author"Kollnberger S."xsd:string
http://purl.uniprot.org/citations/26841353http://purl.uniprot.org/core/author"Price D.A."xsd:string
http://purl.uniprot.org/citations/26841353http://purl.uniprot.org/core/author"Ladell K."xsd:string
http://purl.uniprot.org/citations/26841353http://purl.uniprot.org/core/author"Hatano H."xsd:string
http://purl.uniprot.org/citations/26841353http://purl.uniprot.org/core/author"Wong-Baeza I."xsd:string
http://purl.uniprot.org/citations/26841353http://purl.uniprot.org/core/author"Matthews K.K."xsd:string
http://purl.uniprot.org/citations/26841353http://purl.uniprot.org/core/author"Al-Mossawi H."xsd:string
http://purl.uniprot.org/citations/26841353http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/26841353http://purl.uniprot.org/core/name"Arthritis Rheumatol"xsd:string
http://purl.uniprot.org/citations/26841353http://purl.uniprot.org/core/pages"901-914"xsd:string
http://purl.uniprot.org/citations/26841353http://purl.uniprot.org/core/title"Activation-Induced Killer Cell Immunoglobulin-like Receptor 3DL2 Binding to HLA-B27 Licenses Pathogenic T Cell Differentiation in Spondyloarthritis."xsd:string
http://purl.uniprot.org/citations/26841353http://purl.uniprot.org/core/volume"68"xsd:string
http://purl.uniprot.org/citations/26841353http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/26841353
http://purl.uniprot.org/citations/26841353http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/26841353
http://purl.uniprot.org/uniprot/#_A0A0A7C552-mappedCitation-26841353http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26841353
http://purl.uniprot.org/uniprot/#_A0A0E3DC98-mappedCitation-26841353http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26841353
http://purl.uniprot.org/uniprot/#_A0A0E3DCA0-mappedCitation-26841353http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26841353
http://purl.uniprot.org/uniprot/#_A0A0E3DCA1-mappedCitation-26841353http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26841353
http://purl.uniprot.org/uniprot/#_A0A068B107-mappedCitation-26841353http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26841353
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