ArticleProceedings of the National Academy of Sciences of the United States of America2012
IL-7 receptor blockade reverses autoimmune diabetes by promoting inhibition of effector/memory T cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 141 citations in OpenAlex.
- Trial
- Model-Based Characterization of the Pharmacokinetics, Target Engagement Biomarkers, and Immunomodulatory Activity of PF-06342674, a Humanized mAb Against IL-7 Receptor-α, in Adults with Type 1 Diabetes.The AAPS journal · 2020Trial
- Immunomodulatory activity of humanized anti-IL-7R monoclonal antibody RN168 in subjects with type 1 diabetes.JCI insight · 2019Trial
- Anti-IL-7 receptor α monoclonal antibody (GSK2618960) in healthy subjects - a randomized, double-blind, placebo-controlled study.British journal of clinical pharmacology · 2019Trial
- Remodeling T cell compartments during anti-CD3 immunotherapy of type 1 diabetes.Cellular immunology · 2017Trial
- Cell-intrinsic IL-7Rα deficiency in Foxp3+ Tregs increases type 1 diabetes incidence in NOD mice.ImmunoHorizons · 2026Article
- Insulin enables acquisition of the IL7RCell death & disease · 2026Article
- Patterns of circulating cytokines after 2 types of exercise in active type-1 diabetic patients.Journal of physiology and biochemistry · 2025Article
- Machine learning analysis reveals tumor heterogeneity and stromal-immune niches in breast cancer.NPJ digital medicine · 2025Article
- Role of Interleukins in Type 1 and Type 2 Diabetes.Diagnostics (Basel, Switzerland) · 2025Review
- Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset.Nature communications · 2025Article
- Metformin prevents diabetes development in type 1 diabetes models via suppression of mTOR and STAT3 signaling in immune cells.Scientific reports · 2025Article
- IL-7 in autoimmune diseases: mechanisms and therapeutic potential.Frontiers in immunology · 2025Review
- LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype.Clinical and translational medicine · 2024Article
- Article
- Single-cell profiling reveals unique features of diabetogenic T cells in anti-PD-1-induced type 1 diabetes mice.The Journal of experimental medicine · 2023Article
- Immune-related adverse events after immune check point inhibitors: Understanding the intersection with autoimmunity.Immunological reviews · 2023Review
- IL-7 Deficiency Exacerbates Atopic Dermatitis in NC/Nga Mice.International journal of molecular sciences · 2023Article
- Germline variants associated with toxicity to immune checkpoint blockade.Nature medicine · 2022Article
- Exploring Computational Data Amplification and Imputation for the Discovery of Type 1 Diabetes (T1D) Biomarkers from Limited Human Datasets.Biomolecules · 2022Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 4 countries.
Funding
Abstract
To protect the organism against autoimmunity, self-reactive effector/memory T cells (T(E/M)) are controlled by cell-intrinsic and -extrinsic regulatory mechanisms. However, how some T(E/M) cells escape regulation and cause autoimmune disease is currently not understood. Here we show that blocking IL-7 receptor-α (IL-7Rα) with monoclonal antibodies in nonobese diabetic (NOD) mice prevented autoimmune diabetes and, importantly, reversed disease in new-onset diabetic mice. Surprisingly, IL-7-deprived diabetogenic T(E/M) cells remained present in the treated animals but showed increased expression of the inhibitory receptor Programmed Death 1 (PD-1) and reduced IFN-γ production. Conversely, IL-7 suppressed PD-1 expression on activated T cells in vitro. Adoptive transfer experiments revealed that T(E/M) cells from anti-IL-7Rα-treated mice had lost their pathogenic potential, indicating that absence of IL-7 signals induces cell-intrinsic tolerance. In addition to this mechanism, IL-7Rα blockade altered the balance of regulatory T cells and T(E/M) cells, hence promoting cell-extrinsic regulation and further increasing the threshold for diabetogenic T-cell activation. Our data demonstrate that IL-7 contributes to the pathogenesis of autoimmune diabetes by enabling T(E/M) cells to remain in a functionally competent state and suggest IL-7Rα blockade as a therapy for established T-cell-dependent autoimmune diseases.
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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.