ArticleScientific reports2017
Soluble OX40L and JAG1 Induce Selective Proliferation of Functional Regulatory T-Cells Independent of canonical TCR signaling.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Decoding TNF receptor superfamily control of CD4Cell communication and signaling : CCS · 2026Review
- Single-cell and bulk transcriptomic analyses uncover immune subtypes associated with programmed cell death features in intrahepatic cholangiocarcinoma.Scientific reports · 2026Article
- Constitutively Active Stat5b Expression in Dendritic Cells Enhances Treg-Mediated Elimination of Autoreactive CD8International journal of molecular sciences · 2026Article
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- Pathogenesis of allergic diseases and implications for therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Attenuated IL-2 muteins leverage the TCR signal to enhance regulatory T cell homeostasis and responseFrontiers in immunology · 2023Article
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- OX40L-JAG1-Induced Expansion of Lineage-Stable Regulatory T Cells Involves Noncanonical NF-κB Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Restoring self-tolerance in autoimmune diseases by enhancing regulatory T-cells.Cellular immunology · 2019Review
- Critical role of OX40 signaling in the TCR-independent phase of human and murine thymic Treg generation.Cellular & molecular immunology · 2019Article
- A comprehensive review on the role of co-signaling receptors and Treg homeostasis in autoimmunity and tumor immunity.Journal of autoimmunity · 2018Review
- Identification of a Novel OX40LScientific reports · 2018Article
- Tolerogenic bone marrow-derived dendritic cells induce neuroprotective regulatory T cells in a model of Parkinson's disease.Molecular neurodegeneration · 2018Article
- c-Jun N-terminal kinase 1 defective CD4+CD25+FoxP3+ cells prolong islet allograft survival in diabetic mice.Scientific reports · 2018Article
- Immunomodulatory Bonds of the Partnership between Dendritic Cells and T Cells.Critical reviews in immunology · 2018Review
- The Ox40/Ox40 Ligand Pathway Promotes Pathogenic Th Cell Responses, Plasmablast Accumulation, and Lupus Nephritis in NZB/W F1 Mice.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- PKC-ѳ is dispensable for OX40L-induced TCR-independent Treg proliferation but contributes by enabling IL-2 production from effector T-cells.Scientific reports · 2017Article
- Regulatory T cells in multiple sclerosis and myasthenia gravis.Journal of neuroinflammation · 2017Review
- Overexpression of heparanase enhances T lymphocyte activities and intensifies the inflammatory response in a model of murine rheumatoid arthritis.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
Regulatory T-cells (Tregs) play a pivotal role in maintaining peripheral tolerance. Increasing Treg numbers/functions has been shown to ameliorate autoimmune diseases. However, common Treg expansion approaches use T-Cell Receptor (TCR)-mediated stimulation which also causes proliferation of effector T-cells (Teff). To overcome this limitation, purified patient-specific Tregs are expanded ex vivo and transfused. Although promising, this approach is not suitable for routine clinical use. Therefore, an alternative approach to selectively expand functional Tregs in vivo is highly desired. We report a novel TCR-independent strategy for the selective proliferation of Foxp3+Tregs (without Teff proliferation), by co-culturing CD4+ T-cells with OX40 L+Jagged(JAG)-1+ bone marrow-derived DCs differentiated with GM-CSF or treating them with soluble OX40 L and JAG1 in the presence of exogenous IL-2. Tregs expanded using soluble OX40 L and JAG1 were of suppressive phenotype and delayed the onset of diabetes in NOD mice. Ligation of OX40 L and JAG1 with their cognate-receptors OX40 and Notch3, preferentially expressed on Tregs but not on Teff cells, was required for selective Treg proliferation. Soluble OX40L-JAG1-induced NF-κB activation as well as IL-2-induced STAT5 activation were essential for the proliferation of Tregs with sustained Foxp3 expression. Altogether, these findings demonstrate the utility of soluble OX40 L and JAG1 to induce TCR-independent Treg proliferation.
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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.