ArticleImmunology2009
Interleukin-15 stimulates macrophages to activate CD4+ T cells: a role in the pathogenesis of rheumatoid arthritis?
Article in Immunology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
- Entinostat in combination with nivolumab in metastatic pancreatic ductal adenocarcinoma: a phase 2 clinical trial.Nature communications · 2024Trial
- Molecular Signature and miRNA Pattern of CD4 + T Lymphocytes in Plaque Psoriasis.Clinical reviews in allergy & immunology · 2026Review
- Breaking a dogma: orthodontic tooth movement alters systemic immunity.Progress in orthodontics · 2024Article
- JAK Inhibitors in Rheumatoid Arthritis: Immunomodulatory Properties and Clinical Efficacy.International journal of molecular sciences · 2024Review
- Signalling mechanisms driving homeostatic and inflammatory effects of interleukin-15 on tissue lymphocytes.Discovery immunology · 2024Review
- Meniscus repair via collagen matrix wrapping and bone marrow injection: clinical and biomolecular study.International orthopaedics · 2023Article
- Immune landscape in invasive ductal and lobular breast cancer reveals a divergent macrophage-driven microenvironment.Nature cancer · 2023Article
- Tumor-associated macrophages: Prognostic and therapeutic targets for cancer in humans and dogs.Frontiers in immunology · 2023Review
- Transcriptomic profiling of calcified aortic valves in clonal hematopoiesis of indeterminate potential carriers.Scientific reports · 2022Article
- Recombinant BCG-LTAK63 Vaccine Candidate for Tuberculosis Induces an Inflammatory Profile in Human Macrophages.Vaccines · 2022Article
- Peripheral Blood Inflammation Profile of Patients with Pulmonary Arterial Hypertension Using the High-Throughput Olink Proteomics Platform.American journal of respiratory cell and molecular biology · 2022Article
- The Role of M1/M2 Macrophage Polarization in Rheumatoid Arthritis Synovitis.Frontiers in immunology · 2022Review
- Selective Targeting of IL-15Rα Is Sufficient to Reduce Inflammation.Frontiers in immunology · 2022Article
- A Tale of Two Immune Cells in Rheumatoid Arthritis: The Crosstalk Between Macrophages and T Cells in the Synovium.Frontiers in immunology · 2021Review
- Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- Regulation of T Cell Activities in Rheumatoid Arthritis by the Novel Fusion Protein IgD-Fc-Ig.Frontiers in immunology · 2020Article
- Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS-) vs. Alternatively Activated Macrophages.Frontiers in immunology · 2019Review
- IL-15 regulates susceptibility of CD4Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Active immunization with human interleukin-15 induces neutralizing antibodies in non-human primates.BMC immunology · 2016Article
- Triptolide Modulates TREM-1 Signal Pathway to Inhibit the Inflammatory Response in Rheumatoid Arthritis.International journal of molecular sciences · 2016Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-15 (IL-15) is a proinflammatory cytokine that is overexpressed in rheumatoid arthritis (RA), a disease characterized by activation of monocytes/macrophages (MPhi), and by expansion of autoreactive CD4(+) T cells. We hypothesized that IL-15 plays a major role for this expansion of CD4(+) T cells and modulates the phenotype of monocytes/MPhi and their interaction with CD4(+) T cells. Here, we show that IL-15 enhances the proliferation of CD4(+) T cells from patients with RA in peripheral blood mononuclear cell cocultures. To further dissect the underlying mechanisms, we employed MPhi from IL-15(-/-) or IL-15 transgenic mice. These were induced to differentiate or were stimulated with IL-15. Here we show that addition of IL-15 during differentiation of MPhi (into 'IL-15MPhi') and overexpression of IL-15 by MPhi from IL-15(tg) mice leads to increased levels of major histocompatibility complex class II expression. This resulted in enhanced stimulation of antigen-specific CD4(+) T cells in vitro and was accompanied by reduced messenger RNA expression in MPhi for immunosuppressive SOCS3. The proliferation rates of IL-15MPhi and IL-15(tg)MPhi were high, which was reflected by increased p27(Kip1) and reduced p21(Waf1) levels. In view of high serum and synovial levels of IL-15 in patients with RA, our data suggest the possibility that this excess IL-15 in RA may stimulate monocytes/MPhi to activate the characteristic autoreactive CD4(+) T cells in RA.
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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.