ArticleJCI insight2017
Human regulatory T cells undergo self-inflicted damage via granzyme pathways upon activation.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Immune Tolerance-Adjusted Personalized Immunogenicity Prediction for Pompe Disease.Frontiers in immunology · 2021Trial
- Cell-to-cell variability and gain of methylation at polycomb CpG islands as a hallmark of aging.Nature communications · 2026Article
- Regulatory T cells in breast cancer drivers of immune suppression and targets for immunotherapy.Frontiers in immunology · 2026Review
- Regulatory T cells in intracerebral hemorrhage: mechanisms of immunomodulation and therapeutic potential.Frontiers in immunology · 2026Review
- Interferon-stimulated Viperin impairs Treg function in autoimmune thrombocytopenia.Cell communication and signaling : CCS · 2025Article
- Regulatory T cells and their role in allergic disease.Allergy · 2025Review
- Rewiring immune suppression in NSCLC: Roles and plasticity of Tregs and Th17 cells.Frontiers in immunology · 2025Review
- The pro-tumorigenic roles of granzyme B: mechanisms and therapeutic implications.Frontiers in immunology · 2025Review
- The immunobiology and therapeutic potential of regulatory T cells in autoimmune diseases and allergic diseases.Frontiers in immunology · 2025Review
- Phenotypic profiling of human induced regulatory T cells at early differentiation: insights into distinct immunosuppressive potential.Cellular and molecular life sciences : CMLS · 2024Article
- Tipping the balance in autoimmunity: are regulatory t cells the cause, the cure, or both?Molecular and cellular pediatrics · 2024Review
- Steroid receptor coactivator 3 is a key modulator of regulatory T cell-mediated tumor evasion.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Fluorogenic Granzyme A Substrates Enable Real-Time Imaging of Adaptive Immune Cell Activity.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2023Article
- Fluorogenic Granzyme A Substrates Enable Real-Time Imaging of Adaptive Immune Cell Activity.Angewandte Chemie (International ed. in English) · 2023Article
- Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity.MedComm · 2022Review
- Review
- mTORC1 Inhibition Protects Human Regulatory T Cells From Granzyme-B-Induced Apoptosis.Frontiers in immunology · 2022Article
- Cytolytic CD4Frontiers in immunology · 2022Review
- Lupus susceptibility gene Esrrg modulates regulatory T cells through mitochondrial metabolism.JCI insight · 2021Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 3 institutions in 1 country.
Funding
Abstract
Tregs hold great promise as a cellular therapy for multiple immunologically mediated diseases, given their ability to control immune responses. The success of such strategies depends on the expansion of healthy, suppressive Tregs ex vivo and in vivo following the transfer. In clinical studies, levels of transferred Tregs decline sharply in the blood within a few days of the transfer. Tregs have a high rate of apoptosis. Here, we describe a new mechanism of Treg self-inflicted damage. We show that granzymes A and -B (GrA and GrB), which are highly upregulated in human Tregs upon stimulation, leak out of cytotoxic granules to induce cleavage of cytoplasmic and nuclear substrates, precipitating apoptosis in target cells. GrA and GrB substrates were protected from cleavage by inhibiting granzyme activity in vitro. Additionally, we show - by using cytometry by time of flight (CYTOF) - an increase in GrB-expressing Tregs in the peripheral blood and renal allografts of transplant recipients undergoing rejection. These GrB-expressing Tregs showed an activated phenotype but were significantly more apoptotic than non-GrB expressing Tregs. This potentially novel finding improves our understanding of Treg survival and suggests that manipulating Gr expression or activity might be useful for designing more effective Treg therapies.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.