ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Th17 cells expressing KIR3DL2+ and responsive to HLA-B27 homodimers are increased in ankylosing spondylitis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers, 1 of them a synthesis that pooled it.
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Who cites it
148 citing papers in PubMed, 1 synthesis or guideline pooled it, 297 citations in OpenAlex.
- Imbalance of Peripheral Lymphocyte Subsets in Patients With Ankylosing Spondylitis: A Meta-Analysis.Frontiers in immunology · 2021Pooled it
- Effect of Secukinumab on Patient-Reported Outcomes in Patients With Active Ankylosing Spondylitis: A Phase III Randomized Trial (MEASURE 1).Arthritis & rheumatology (Hoboken, N.J.) · 2016Trial
- Mechanistic Insights from Human Studies in Axial Spondyloarthritis: A T Cell Story.Current rheumatology reports · 2026Review
- Comprehensive overview of alternative medicine in the treatment of ankylosing spondylitis: Symptoms, pathogenesis, diagnosis and treatments (Review).Biomedical reports · 2026Review
- Killer cell immunoglobulin-like receptor (KIR) alleles suggested to be associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).Brain, behavior, and immunity · 2025Article
- Bimekizumab in the Treatment of Axial Spondyloarthritis and Psoriatic Arthritis: A New Kid on the Block.International journal of molecular sciences · 2025Review
- HLA-B27 and spondyloarthritis: at the crossroads of innate and adaptive immunity.Nature reviews. Rheumatology · 2025Review
- Beyond the joints: mechanistic insights and multidisciplinary strategies for spondyloarthritis-associated uveitis.Frontiers in immunology · 2025Review
- Inhibitory KIRs decrease HLA class II-mediated protection in Type 1 Diabetes.PLoS genetics · 2024Article
- An Uncommon Overlap Syndrome Between Ankylosing Spondylitis and Amyotrophic Lateral Sclerosis-Case Report.Medicina (Kaunas, Lithuania) · 2024Article
- Axial Spondyloarthritis: an overview of the disease.Rheumatology international · 2024Review
- Dysregulated Non-Coding RNA Expression in T Cells from Patients with Ankylosing Spondylitis Contributes to Its Immunopathogenesis.Biomedicines · 2024Review
- Environmental and Genetic Determinants of Ankylosing Spondylitis.International journal of molecular sciences · 2024Review
- Autoimmune diseases: targets, biology, and drug discovery.Acta pharmacologica Sinica · 2024Review
- Review
- Cell Surface B2m-Free Human Leukocyte Antigen (HLA) Monomers and Dimers: Are They Neo-HLA Class and Proto-HLA?Biomolecules · 2023Review
- Human Leukocyte Antigen B27-Negative Axial Spondyloarthritis: What Do We Know?ACR open rheumatology · 2023Review
- KIR-HLA interactions extend human CD8+ T cell lifespan in vivo.The Journal of clinical investigation · 2023Article
- Non-Classical HLA Class 1b and Hepatocellular Carcinoma.Biomedicines · 2023Review
- Identification of potential biomarkers for ankylosing spondylitis based on bioinformatics analysis.BMC musculoskeletal disorders · 2023Article
88 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.