ArticleAnnals of the rheumatic diseases2020
Normal human enthesis harbours conventional CD4+ and CD8+ T cells with regulatory features and inducible IL-17A and TNF expression.
Article in Annals of the rheumatic diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42 citing papers in PubMed, 87 citations in OpenAlex.
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- IL-23 drives uveitis by acting on a population of tissue-resident entheseal T cells.JCI insight · 2025Article
- Genetically predicted immune cells mediates the association between hepatocellular carcinoma and inflammatory proteins: a Mendelian randomization study.Discover oncology · 2025Article
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- Exploring T Cell and NK Cell Involvement in Ankylosing Spondylitis Through Single-Cell Sequencing.Journal of cellular and molecular medicine · 2024Article
- Single-cell RNA-sequencing analysis of immune and mesenchymal cell crosstalk in the developing enthesis.Scientific reports · 2024Article
- Patients with ankylosing spondylitis present a distinct CD8 T cell subset with osteogenic and cytotoxic potential.RMD open · 2024Article
- From PsO to PsA: the role of TFrontiers in medicine · 2024Review
- Early psoriatic arthritis: when is the right time to start advanced therapy?Therapeutic advances in musculoskeletal disease · 2024Review
- Lymphocyte homing and recirculation with tumor tertiary lymphoid structure formation: predictions for successful cancer immunotherapy.Frontiers in immunology · 2024Review
- Review
- The bone marrow side of axial spondyloarthritis.Nature reviews. Rheumatology · 2023Review
- Cytokines in Spondyloarthritis and Inflammatory Bowel Diseases: From Pathogenesis to Therapeutic Implications.International journal of molecular sciences · 2023Review
- Oxygen microcapsules improve immune checkpoint blockade by ameliorating hypoxia condition in pancreatic ductal adenocarcinoma.Bioactive materials · 2023Article
- Janus Kinase Inhibitors: A New Tool for the Treatment of Axial Spondyloarthritis.International journal of molecular sciences · 2023Review
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Authors and funding
21 authors at 5 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe human enthesis conventional T cells are poorly characterised.
objectivesTo study the biology of the conventional T cells in human enthesis.
methodsCD4+ and CD8+ T cells were investigated in 25 enthesis samples using immunofluorescence, cytometrically, bulk RNAseq and quantitative real-time PCR following anti-CD3/CD28 bead stimulation to determine interleukin (IL)-17A and tumour necrosis factor (TNF) levels. T-cell receptor (TCR) repertoires were characterised and a search for putative T-cell reactivity was carried out using TCR3 database. The impact of pharmacological antagonism with retinoic acid receptor-related orphan nuclear receptor gamma t inhibitor (RORγti), methotrexate and phosphodiesterase type 4 inhibitor (PDE4i) was investigated.
resultsImmunofluorescence and cytometry suggested entheseal resident CD4+ and CD8+ T cells with a resident memory phenotype (CD69+/CD45RA-) and tissue residency gene transcripts (higher NR4A1/AhR and lower KLF2/T-bet transcripts). Both CD4+ and CD8+ T cells showed increased expression of immunomodulatory genes including IL-10 and TGF-β compared with peripheral blood T cells with entheseal CD8+ T cells having higher CD103, CD49a and lower SIPR1 transcript that matched CD4+ T cells. Following stimulation, CD4+ T cells produced more TNF than CD8+ T cells and IL-17A was produced exclusively by CD4+ T cells. RNAseq suggested both Cytomegalovirus and influenza A virus entheseal resident T-cell clonotype reactivity. TNF and IL-17A production from CD4+ T cells was effectively inhibited by PDE4i, while RORγti only reduced IL-17A secretion.
conclusionsHealthy human entheseal CD4+ and CD8+ T cells exhibit regulatory characteristics and are predicted to exhibit antiviral reactivity with CD8+ T cells expressing higher levels of transcripts suggestive of tissue residency. Inducible IL-17A and TNF production can be robustly inhibited in vitro.
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