ArticleThe Journal of clinical investigation2018
Nox2 in regulatory T cells promotes angiotensin II-induced cardiovascular remodeling.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 60 citations in OpenAlex.
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- Regulatory T cells in cardiac allograft vasculopathy: from mechanistic insights to clinical tolerance.Frontiers in immunology · 2026Review
- Signaling Pathways of the Acquired Immune System and Myocardial Dysfunction in Chronic Kidney Disease-What Do We Know So Far?Biomolecules · 2025Review
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Reactive oxygen species in hypertension.Nature reviews. Cardiology · 2025Review
- Iron and energy metabolic interactions in Treg-mediated immune regulation.Frontiers in immunology · 2025Review
- Immune mechanisms in the pathophysiology of hypertension.Nature reviews. Nephrology · 2024Review
- Overview of multifunctional Tregs in cardiovascular disease: From insights into cellular functions to clinical implications.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- The Role of Regulatory T Cells and Their Therapeutic Potential in Hypertensive Disease of Pregnancy: A Literature Review.International journal of molecular sciences · 2024Review
- Immune cells and hypertension.Immunologic research · 2024Review
- Functional NADPH oxidase 2 in T cells amplifies salt-sensitive hypertension and associated renal damage.American journal of physiology. Renal physiology · 2023Article
- Metabolic regulation of forkhead box P3 alternative splicing isoforms and their impact on health and disease.Frontiers in immunology · 2023Review
- Immunoregulation: the interplay between metabolism and redox homeostasis.Frontiers in transplantation · 2023Review
- Targeting regulatory T cells for cardiovascular diseases.Frontiers in immunology · 2023Review
- NADPH Oxidases in Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction.Antioxidants (Basel, Switzerland) · 2022Review
- Perivascular Fibrosis Is Mediated by a KLF10-IL-9 Signaling Axis in CD4+ T Cells.Circulation research · 2022Article
- Mosaic theory revised: inflammation and salt play central roles in arterial hypertension.Cellular & molecular immunology · 2022Review
- Central role of c-Src in NOX5- mediated redox signalling in vascular smooth muscle cells in human hypertension.Cardiovascular research · 2022Article
- Developmental endothelial locus-1 protects from hypertension-induced cardiovascular remodeling via immunomodulation.The Journal of clinical investigation · 2022Article
- Oxidative Stress in Arterial Hypertension (HTN): The Nuclear Factor Erythroid Factor 2-Related Factor 2 (Nrf2) Pathway, Implications and Future Perspectives.Pharmaceutics · 2022Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
The superoxide-generating enzyme Nox2 contributes to hypertension and cardiovascular remodeling triggered by activation of the renin-angiotensin system. Multiple Nox2-expressing cells are implicated in angiotensin II-induced (Ang II-induced) pathophysiology, but the importance of Nox2 in leukocyte subsets is poorly understood. Here, we investigated the role of Nox2 in T cells, particularly Tregs. Mice globally deficient in Nox2 displayed increased numbers of Tregs in the heart at baseline, whereas Ang II-induced effector T cell (Teff) infiltration was inhibited. To investigate the role of Treg Nox2, we generated a mouse line with CD4-targeted Nox2 deficiency (Nox2fl/flCD4Cre+). These animals showed inhibition of Ang II-induced hypertension and cardiac remodeling related to increased tissue-resident Tregs and reduction in infiltrating Teffs, including Th17 cells. The protection in Nox2fl/flCD4Cre+ mice was reversed by anti-CD25 antibody depletion of Tregs. Mechanistically, Nox2-/y Tregs showed higher in vitro suppression of Teff proliferation than WT Tregs, increased nuclear levels of FoxP3 and NF-κB, and enhanced transcription of CD25, CD39, and CD73. Adoptive transfer of Tregs confirmed that Nox2-deficient cells had greater inhibitory effects on Ang II-induced heart remodeling than WT cells. These results identify a previously unrecognized role of Nox2 in modulating suppression of Tregs, which acts to enhance hypertension and cardiac remodeling.
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Registered trials
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