{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:38:39Z","timestamp":1791275919175,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,3,28]],"date-time":"2016-03-28T00:00:00Z","timestamp":1459123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Oxford NIHR Biomedical Research Centre"},{"name":"Oxford NIHR Biomedical Research Unit"},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Mexican National Council of Science and Technology"},{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Wellcome Trust. Dr. Price is a Wellcome Trust Senior Investigator."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      <jats:bold>In the<\/jats:bold>\n                      <jats:bold>spondyloarthritides (SpA), increased numbers of CD4+ T cells express killer cell immunoglobulin\u2010like receptor 3DL2 (KIR\u20103DL2). The aim of this study was to determine the factors that induce KIR\u20103DL2 expression, and to characterize the relationship between HLA\u2013B27 and the phenotype and function of KIR\u20103DL2\u2013expressing CD4+ T cells in SpA.<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:bold>In total, 34 B27+<\/jats:bold>\n                      <jats:bold>patients with SpA, 28 age\u2010 and sex\u2010matched healthy controls (20 B27\u2212 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\u2010switch anchored reverse transcription\u2013polymerase chain reaction and sequencing analysis. Cytokines were measured by enzyme\u2010linked immunosorbent assay.<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cellular activation induced KIR\u20103DL2 expression on both naive and effector CD4+ T cells. KIR\u20103DL2 binding to B27+ cells promoted expression of KIR\u20103DL2, the Th17\u2010specific transcription factor retinoic acid receptor\u2013related orphan nuclear receptor \u03b3t, and the antiapoptotic factor B cell lymphoma 2. KIR\u20103DL2+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\u2010presenting cells, KIR\u20103DL2+CD4+ T cells produced less interleukin\u20102 (IL\u20102) but more IL\u201017. This effect was blocked by HC10, an antibody that inhibits the binding of KIR\u20103DL2 to B27 heavy chains.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>KIR\u20103DL2 binding to HLA\u2013B27 licenses Th17 cell differentiation in SpA. These findings raise the therapeutic potential of targeting HLA\u2013B27\u2013KIR\u20103DL2 interactions for the treatment of B27+ patients with SpA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.39515","type":"journal-article","created":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T11:26:25Z","timestamp":1448450785000},"page":"901-914","source":"Crossref","is-referenced-by-count":47,"title":["Activation\u2010Induced Killer Cell Immunoglobulin\u2010like Receptor 3DL2 Binding to HLA\u2013B27 Licenses Pathogenic T Cell Differentiation in Spondyloarthritis"],"prefix":"10.1002","volume":"68","author":[{"given":"Anna","family":"Ridley","sequence":"first","affiliation":[{"name":"Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Hatano","sequence":"additional","affiliation":[{"name":"Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Wong\u2010Baeza","sequence":"additional","affiliation":[{"name":"Isabel Wong\u2010Baeza, PhD: Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford, UK, and National School of Biological Sciences, National Polytechnic Institute Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Shaw","sequence":"additional","affiliation":[{"name":"Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine K.","family":"Matthews","sequence":"additional","affiliation":[{"name":"QIMR, Berghofer Medical Research Institute Brisbane Queensland 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