ArticleProceedings of the National Academy of Sciences of the United States of America2007
Nitric oxide induces CD4+CD25+ Foxp3 regulatory T cells from CD4+CD25 T cells via p53, IL-2, and OX40.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 155 citations in OpenAlex.
- The potential role of S-nitrosoglutathione reductase in astrocyte BAFF expression and B cell activation in experimental autoimmune encephalomyelitis.Journal of neuroimmunology · 2026Article
- Immunomodulatory and anti-inflammatory potential of S-nitrosoglutathione (GSNO) in multiple sclerosis: a review of mechanisms and therapeutic perspectives.Frontiers in immunology · 2026Review
- AT2R activation reduces M1-type macrophages and promotes tregs accumulation in ischemia-reperfusion-induced acute kidney injury.Frontiers in pharmacology · 2026Article
- Therapeutic potential of S-nitrosoglutathione reductase inhibitor in B cell-driven experimental autoimmune encephalomyelitis.Journal of neuroimmunology · 2025Article
- Maintenance of graft tissue-resident Foxp3+ cells is necessary for lung transplant tolerance in mice.The Journal of clinical investigation · 2025Article
- Regulatory T cells in solid tumor immunotherapy: effect, mechanism and clinical application.Cell death & disease · 2025Review
- The role of S-nitrosoglutathione reductase (GSNOR) in T cell-mediated immunopathology of experimental autoimmune encephalomyelitis (EAE).Neuroscience · 2025Article
- Tumor NOS2 and COX2 Spatial Juxtaposition with CD8+ T Cells Promote Metastatic and Cancer Stem Cell Niches that Lead to Poor Outcome in ER- Breast Cancer.Cancer research communications · 2024Article
- Inhibitors of NLRP3 Inflammasome Formation: A Cardioprotective Role for the Gasotransmitters Carbon Monoxide, Nitric Oxide, and Hydrogen Sulphide in Acute Myocardial Infarction.International journal of molecular sciences · 2024Review
- Targeting amino acid-metabolizing enzymes for cancer immunotherapy.Frontiers in immunology · 2024Review
- Gut redox and microbiome: charting the roadmap to T-cell regulation.Frontiers in immunology · 2024Review
- The Macrophage Activator GcMAF-RF Enhances the Antitumor Effect of Karanahan Technology through Induction of M2-M1 Macrophage Reprogramming.Journal of immunology research · 2024Article
- NOS2 and COX2 Provide Key Spatial Targets that Determine Outcome in ER- Breast Cancer.bioRxiv : the preprint server for biology · 2023Article
- Amino acid metabolism reprogramming: shedding new light on T cell anti-tumor immunity.Journal of experimental & clinical cancer research : CR · 2023Review
- Biopterin metabolism and nitric oxide recoupling in cancer.Frontiers in oncology · 2023Review
- Opportunities for Nitric Oxide in Potentiating Cancer Immunotherapy.Pharmacological reviews · 2022Review
- Photoaging: UV radiation-induced inflammation and immunosuppression accelerate the aging process in the skin.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Review
- The lymphatic vasculature: An active and dynamic player in cancer progression.Medicinal research reviews · 2022Review
- Dysregulation of Survivin-Targeting microRNAs in Autoimmune Diseases: New Perspectives for Novel Therapies.Frontiers in immunology · 2022Review
- Regulation of T Cells in Cancer by Nitric Oxide.Cells · 2021Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
The principal aim of the immune system is to establish a balance between defense against pathogens and avoidance of autoimmune disease. This balance is achieved partly through regulatory T cells (Tregs). CD4(+)CD25(+) Tregs are either naturally occurring or induced by antigens and are characterized by the expression of the X-linked forkhead/winged helix transcription factor, Foxp3. Here we report a previously unrecognized subset of CD4(+)CD25(+) Tregs derived from CD4(+)CD25(-) T cells induced by nitric oxide (NO). The induction of Tregs (NO-Tregs) is independent of cGMP but depends on p53, IL-2, and OX40. NO-Tregs produced IL-4 and IL-10, but not IL-2, IFNgamma, or TGFbeta. The cells were GITR(+), CD27(+), T-bet(low), GATA3(high), and Foxp3(-). NO-Tregs suppressed the proliferation of CD4(+)CD25(-) T cells in vitro and attenuated colitis- and collagen-induced arthritis in vivo in an IL-10-dependent manner. NO-Tregs also were induced in vivo in SCID mice adoptively transferred with CD4(+)CD25(-) T cells in the presence of LPS and IFNgamma, and the induction was completely inhibited by N(G)-monomethyl-L-arginine, a pan NO synthase inhibitor. Therefore, our findings uncovered a previously unrecognized function of NO via the NO-p53-IL-2-OX40-survivin signaling pathway for T cell differentiation and development.
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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.