ArticleAutoimmunity2016
Age-dependent divergent effects of OX40L treatment on the development of diabetes in NOD mice.
Article in Autoimmunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 26 citations in OpenAlex.
- Association between OX40L polymorphism and type 2 diabetes mellitus in Iranians.BMC medical genomics · 2024Article
- OX40L-JAG1-Induced Expansion of Lineage-Stable Regulatory T Cells Involves Noncanonical NF-κB Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Critical role of OX40 signaling in the TCR-independent phase of human and murine thymic Treg generation.Cellular & molecular immunology · 2019Article
- Increased Expressions of OX40 and OX40 Ligand in Patients with Primary Immune Thrombocytopenia.Journal of immunology research · 2019Article
- Enhancement of the Soluble Form of OX40 and OX40L Costimulatory Molecules but Reduction of the Membrane Form in Type 1 Diabetes (T1D).Journal of immunology research · 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
- Trivalent soluble TNF Receptor, a potent TNF-α antagonist for the treatment collagen-induced arthritis.Scientific reports · 2018Article
- Silibinin alleviates inflammation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes and has a therapeutic effect on arthritis in rats.Scientific reports · 2018Article
- Mesenchymal stem cells ameliorate experimental arthritis via expression of interleukin-1 receptor antagonist.PloS one · 2018Article
- Euglena gracilis Z and its carbohydrate storage substance relieve arthritis symptoms by modulating Th17 immunity.PloS one · 2018Article
- Effect of Qianghuo Erhuang Decoction on T Regulatory and T Helper 17 Cells in Treatment of Adjuvant-induced Arthritis in Rats.Scientific reports · 2017Article
- 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
- Regulatory T cells in multiple sclerosis and myasthenia gravis.Journal of neuroinflammation · 2017Review
- CD137 Plays Both Pathogenic and Protective Roles in Type 1 Diabetes Development in NOD Mice.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Overexpression of heparanase enhances T lymphocyte activities and intensifies the inflammatory response in a model of murine rheumatoid arthritis.Scientific reports · 2017Article
- Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis.Scientific reports · 2017Article
- Soluble OX40L and JAG1 Induce Selective Proliferation of Functional Regulatory T-Cells Independent of canonical TCR signaling.Scientific reports · 2017Article
- Carbidopa, a drug in use for management of Parkinson disease inhibits T cell activation and autoimmunity.PloS one · 2017Article
- Increased expression of Th17 cytokines and interleukin-22 correlates with disease activity in pristane-induced arthritis in rats.PloS one · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Earlier, we have shown that GM-CSF derived bone marrow (BM) dendritic cells (G-BMDCs) can expand Foxp3(+) regulatory T-cells (Tregs) through a TCR-independent, but IL-2 dependent mechanism that required OX40L/OX40 interaction. While some reports have shown suppression of autoimmunity upon treatment with an OX40 agonist, others have shown exacerbation of autoimmune disease instead. To better understand the basis for these differing outcomes, we compared the effects of OX40L treatment in 6-week-old pre-diabetic and 12-week-old near diabetic NOD mice. Upon treatment with OX40L, 6-week-old NOD mice remained normoglycemic and showed a significant increase in Tregs in their spleen and lymph nodes, while 12-week-old NOD mice very rapidly developed hyperglycemia and failed to show Treg increase in spleen or LN. Interestingly, OX40L treatment increased Tregs in the thymus of both age groups. However, it induced Foxp3(+)CD103(+)CD38(-) stable-phenotype Tregs in the thymus and reduced the frequency of autoreactive Teff cells in 6-week-old mice; while it induced Foxp3(+)CD103(-)CD38(+) labile-phenotype Tregs in the thymus and increased autoreactive CD4(+) T cells in the periphery of 12-week-old mice. This increase in autoreactive CD4(+) T cells was likely due to either a poor suppressive function or conversion of labile Tregs into Teff cells. Using ex vivo cultures, we found that the reduction in Treg numbers in 12-week-old mice was likely due to IL-2 deficit, and their numbers could be increased upon addition of exogenous IL-2. The observed divergent effects of OX40L treatment were likely due to differences in the ability of 6- and 12-week-old NOD mice to produce IL-2.
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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.