ArticleJCI insight2021
IL-35 promotes CD4+Foxp3+ Tregs and inhibits atherosclerosis via maintaining CCR5-amplified Treg-suppressive mechanisms.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Systematic Review of Interleukin-35 in Endothelial Dysfunction: A New Target for Therapeutic Intervention.Mediators of inflammation · 2025Pooled it
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- Functional Heterogeneity of Immune Cell Subpopulations in Atherosclerosis: From Basic Mechanisms to Precision Therapy.Reviews in cardiovascular medicine · 2026Review
- Compensatory relationships determine the impact of TGF-β on the humoral immune response to hepatitis B surface antigen.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Novel Organelle-Based Intracellular Immunity with Mechanistic and Therapeutic Implications.Barrier immunity · 2026Article
- Impaired IL-35/Treg Axis Facilitates Neuropathic Pain Via TNF-α, TLR4, and HMGB1 Activation.Immunity, inflammation and disease · 2026Article
- TGF-β-induced Tregs release extracellular vesicles that modulate CD4+ T-cell proliferation and phenotype in a Nrp1-dependent manner.ImmunoHorizons · 2026Article
- The role and mechanism of IL‑35 in myasthenia gravis (Review).International journal of molecular medicine · 2026Review
- A comprehensive analysis of immune checkpoint receptor-ligand pairs in aortic diseases highlights the immunosuppressive roles of CD155 and CD274.Genes & diseases · 2026Article
- Cytokines Associated with Activation of CD4International journal of molecular sciences · 2026Review
- Targeting inflammatory microenvironments: overcoming therapy resistance and immunosuppression.Molecular cancer · 2026Review
- Regulatory T cells and peripheral immune tolerance: key mechanisms and therapeutic strategies for cardiovascular diseases.Frontiers in immunology · 2026Review
- Discovery of Seven ROS-Sensitive Immune Checkpoints and 46 Ligands Mediating Immune Suppression Through T cell-APC Networks.Journal of Cancer · 2026Article
- Reduced R-loop abundance at proinflammatory loci: a shared epigenetic mechanism in inflammatory and metabolic diseases.Frontiers in cardiovascular medicine · 2026Article
- Regulatory T cells in cardiac allograft vasculopathy: from mechanistic insights to clinical tolerance.Frontiers in immunology · 2026Review
- Exploring the Immunomodulatory Role of Forkhead Box Protein 3 (FOXP3) in the Pathophysiology of Neuropsychiatric Disorders.Molecular neurobiology · 2025Review
- How lactate and lactylation shape the immunity system in atherosclerosis (Review).International journal of molecular medicine · 2025Review
- Interleukin-35 impairs human NK cell effector functions and induces their ILC1-like conversion with tissue residency features.Nature communications · 2025Article
- Pro-Resolving Macrophage-Induced IL-35International journal of molecular sciences · 2025Article
- Alzheimer's disease as an auto-innate immune pathology with potential cell trans-differentiation and enhanced trained immunity in 3xTg-AD mouse model.Journal of Alzheimer's disease : JAD · 2025Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Tregs play vital roles in suppressing atherogenesis. Pathological conditions reshape Tregs and increase Treg-weakening plasticity. It remains unclear how Tregs preserve their function and how Tregs switch into alternative phenotypes in the environment of atherosclerosis. In this study, we observed a great induction of CD4+Foxp3+ Tregs in the spleen and aorta of ApoE-/- mice, accompanied by a significant increase of plasma IL-35 levels. To determine if IL-35 devotes its role in the rise of Tregs, we generated IL-35 subunit P35-deficient (IL-35P35-deficient) mice on an ApoE-/- background and found Treg reduction in the spleen and aorta compared with ApoE-/- controls. In addition, our RNA sequencing data show the elevation of a set of chemokine receptor transcripts in the ApoE-/- Tregs, and we have validated higher CCR5 expression in ApoE-/- Tregs in the presence of IL-35 than in the absence of IL-35. Furthermore, we observed that CCR5+ Tregs in ApoE-/- have lower Treg-weakening AKT-mTOR signaling, higher expression of inhibitory checkpoint receptors TIGIT and PD-1, and higher expression of IL-10 compared with WT CCR5+ Tregs. In conclusion, IL-35 counteracts hyperlipidemia in maintaining Treg-suppressive function by increasing 3 CCR5-amplified mechanisms, including Treg migration, inhibition of Treg weakening AKT-mTOR signaling, and promotion of TIGIT and PD-1 signaling.
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What Socratic holds
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 Socratic graph.