ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Synovial Regulatory T Cells Occupy a Discrete TCR Niche in Human Arthritis and Require Local Signals To Stabilize FOXP3 Protein Expression.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- The Proportion of Regulatory T Cells in Patients with Rheumatoid Arthritis: A Meta-Analysis.PloS one · 2016Pooled it
- The anti-inflammatory potential of nicotinamide (vitamin B3) in JIA: modulating Treg numbers and function with nicotinamide.Arthritis research & therapy · 2026Trial
- Regulatory T cells as a potential treatment for autoimmune inflammatory rheumatic and musculoskeletal diseases.Clinical rheumatology · 2026Review
- Decoding Treg diversity and dysfunction to advance Treg-based therapies in autoimmune and inflammatory diseases.Frontiers in immunology · 2026Review
- Single-cell landscape of immunological responses in patients with juvenile idiopathic arthritis.Genes & diseases · 2025Article
- Peripheral blood regulatory T cells and disease activity, quality of life, and outcomes in children with juvenile idiopathic arthritis.Pediatric rheumatology online journal · 2024Article
- Autoimmunity and Carcinogenesis: Their Relationship under the Umbrella of Autophagy.Biomedicines · 2023Review
- Article
- Juvenile idiopathic arthritis.Nature reviews. Disease primers · 2022Review
- Autoimmunity and Cancer-Two Sides of the Same Coin.Frontiers in immunology · 2022Review
- Th1 polarization defines the synovial fluid T cell compartment in oligoarticular juvenile idiopathic arthritis.JCI insight · 2021Article
- From stability to dynamics: understanding molecular mechanisms of regulatory T cells through Foxp3 transcriptional dynamics.Clinical and experimental immunology · 2019Review
- Bacillus Calmette-Guérin Induces PD-L1 Expression on Antigen-Presenting Cells via Autocrine and Paracrine Interleukin-STAT3 Circuits.Scientific reports · 2019Article
- Targeting Tregs in Juvenile Idiopathic Arthritis and Juvenile Dermatomyositis-Insights From Other Diseases.Frontiers in immunology · 2019Review
- T-Cell Compartmentalization and Functional Adaptation in Autoimmune Inflammation: Lessons From Pediatric Rheumatic Diseases.Frontiers in immunology · 2019Review
- Effector Functions of CD4+ T Cells at the Site of Local Autoimmune Inflammation-Lessons From Rheumatoid Arthritis.Frontiers in immunology · 2019Review
- Nanoparticle-Fusion Protein Complexes Protect against Mycobacterium tuberculosis Infection.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Foxp3 Molecular Dynamics in Treg in Juvenile Idiopathic Arthritis.Frontiers in immunology · 2018Review
- Mucosal Delivery of Fusion Proteins withFrontiers in immunology · 2018Article
- CD161Frontiers in immunology · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
Although there is great interest in harnessing the immunosuppressive potential of FOXP3(+) regulatory T cells (Tregs) for treating autoimmunity, a sizeable knowledge gap exists regarding Treg fate in human disease. In juvenile idiopathic arthritis (JIA) patients, we have previously reported that atypical CD25(+)FOXP3(-) Treg-like cells uniquely populate the inflamed site. Intriguingly, their proportions relative to CD25(+)FOXP3(+) Tregs associate with arthritis course, suggesting a role in disease. The ontogeny of these FOXP3(-) Treg-like cells is, however, unknown. In this study, we interrogated clonal relationships between CD4(+) T cell subsets in JIA, using high-throughput TCR repertoire analysis. We reveal that FOXP3(+) Tregs possess highly exclusive TCRβ usage from conventional T cells, in blood, and also at the inflamed site, where they are clonally expanded. Intriguingly, the repertoires of FOXP3(+) Tregs in synovial fluid are highly overlapping with CD25(+)FOXP3(-) Treg-like cells, indicating fluctuations in FOXP3 expression in the inflamed joint. Furthermore, cultured synovial Tregs rapidly downregulated FOXP3 protein (but not mRNA), and this process was prevented by addition of synovial fluid from JIA patients, through an IL-6-independent mechanism. Our findings suggest that most Tregs arise from a separate lineage from conventional T cells, and that this repertoire divergence is largely maintained under chronic inflammatory conditions. We propose that subsequent Treg expansions at the inflamed site creates an environment that leads to competition for limited resources within the synovium, resulting in the destabilization of FOXP3 expression in some Tregs.
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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.