ArticleJCI insight2019
Critical role of Interleukin 21 and T follicular helper cells in hypertension and vascular dysfunction.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- A Five-Year Prospective, Randomized, Open-Label Study of Standard-Dose Versus Low-Dose Prolonged-Release Tacrolimus With or Without Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker Post Kidney Transplantation.Clinical transplantation · 2025Trial
- Tissue Sodium in Patients With Early Stage Hypertension: A Randomized Controlled Trial.Journal of the American Heart Association · 2022Trial
- Role of vascular smooth muscle cell pathobiology in sepsis‑induced vasoplegia (Review).International journal of molecular medicine · 2026Review
- Hypertension-Induced Renal Injury: From Pathophysiology to Therapeutic Perspectives.Biomedicines · 2026Review
- Recent advances on immunity and hypertension: the new cells on the kidney block.American journal of physiology. Renal physiology · 2025Review
- Exploration of potential biomarkers and immune cell infiltration characteristics for peripheral atherosclerosis in sjögren's syndrome based on comprehensive bioinformatics analysis and machine learning.Frontiers in genetics · 2025Article
- Follicular Helper T Cells: Potential Interventional Targets in Atherosclerosis.Journal of immunology research · 2025Review
- T follicular helper cell is essential for M2 macrophage polarization and pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension.Respiratory research · 2024Article
- Immune mechanisms in the pathophysiology of hypertension.Nature reviews. Nephrology · 2024Review
- Immunomodulatory Activity of Cytokines in Hypertension: A Vascular Perspective.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Immune and inflammatory mechanisms in hypertension.Nature reviews. Cardiology · 2024Review
- Discovering Inflammation in Atherosclerosis: Insights from Pathogenic Pathways to Clinical Practice.International journal of molecular sciences · 2024Review
- Plasma Biomarkers for Hypertension-Mediated Organ Damage Detection: A Narrative Review.Biomedicines · 2024Review
- The Role of Pro-Inflammatory Cytokines in the Pathogenesis of Cardiovascular Disease.International journal of molecular sciences · 2024Review
- Depletion of follicular B cell-derived antibody secreting cells does not attenuate angiotensin II-induced hypertension or vascular compliance.Frontiers in cardiovascular medicine · 2024Article
- The immunology of heart failure with preserved ejection fraction.Clinical science (London, England : 1979) · 2023Review
- A new face among our Associate Editors.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Article
- Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Immune Profiling Reveals Decreases in Circulating Regulatory and Exhausted T Cells in Human Hypertension.JACC. Basic to translational science · 2023Article
- Single cell transcriptome analyses reveal the roles of B cells in fructose-induced hypertension.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
Abstract
T and B cells have been implicated in hypertension, but the mechanisms by which they produce a coordinated response is unknown. T follicular helper (Tfh) cells that produce interleukin 21 (IL21) promote germinal center (GC) B cell responses leading to immunoglobulin (Ig) production. Here we investigate the role of IL21 and Tfh cells in hypertension. In response to angiotensin (Ang) II-induced hypertension, T cell IL21 production is increased, and Il21-/- mice develop blunted hypertension, attenuated vascular end-organ damage, and decreased interleukin 17A (IL17A) and interferon gamma production. Tfh-like cells and GC B cells accumulate in the aorta and plasma IgG1 is increased in hypertensive WT but not Il21-/-mice. Furthermore, Tfh cell deficient mice develop blunted hypertension and vascular hypertrophy in response to Ang II infusion. Importantly, IL21 neutralization reduces blood pressure (BP) and reverses endothelial dysfunction and vascular inflammation. Moreover, recombinant IL21 impairs endothelium-dependent relaxation ex vivo and decreases nitric oxide production from cultured endothelial cells. Finally, we show in humans that peripheral blood T cell production of IL21 correlates with systolic BP and IL17A production. These data suggest that IL21 may be a novel therapeutic target for the treatment of hypertension and its micro- and macrovascular complications.
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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.