ArticleDiabetes2023
Treg-Specific CD226 Deletion Reduces Diabetes Incidence in NOD Mice by Improving Regulatory T-Cell Stability.
Article in Diabetes, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Impaired regulatory T-cell-mediated immune tolerance promotes neurodegeneration in glaucoma.medRxiv : the preprint server for health sciences · 2026Article
- Reduced TIGIT Expression on T Cells Links Hyperglycemia to Immune Dysregulation in Type 1 Diabetes.Cells · 2026Article
- A microenvironment-driven HLA-II-associated insulin neoantigen elicits persistent memory T cell activation in diabetes.Nature immunology · 2026Article
- Abnormal Elevation of the Expression of Costimulatory Molecule CD226 in Graves' DiseaseEndocrine, metabolic & immune disorders drug targets · 2026Article
- Extracellular vesicles fromFrontiers in immunology · 2026Article
- Imbalance of stem-like and effector T cell states in children with early type 1 diabetes across conventional and regulatory subsets.Nature communications · 2025Article
- Human stem cell-derived β cells expressing an optimized CD155 reduce cytotoxic immune cell function for application in type 1 diabetes.Science advances · 2025Article
- Clinical significance of CD155 expression and correlation with immune cell infiltration in triple-negative breast cancer.Translational cancer research · 2025Article
- αTIGIT-IL2 achieves tumor regression by promoting tumor-infiltrating regulatory T cell fragility in mouse models.Nature communications · 2025Article
- Genome-Wide Aggregated Trans Effects Analysis for Circulating Proteins Indicates a Key Role of Immune Checkpoints in Type 1 Diabetes.Diabetes · 2025Article
- TYK2 inhibition enhances Treg differentiation and function while preventing Th1 and Th17 differentiation.Cell reports. Medicine · 2025Article
- The Immune Regulatory Functions of CD226 and Its Implications in Immune-Mediated Diseases.Biomolecules · 2025Review
- Inhibition of CD226 co-stimulation suppresses diabetes development in the NOD mouse by augmenting regulatory T cells and diminishing effector T cell function.Diabetologia · 2025Article
- Blockade of CD155 and CD276 by Monoclonal Antibodies Fosters Immune Tolerance and Promotes Stable Engraftment of iPSC-Derived Islets in Allogeneic Humanized Mice.Transplant international : official journal of the European Society for Organ Transplantation · 2025Article
- The perfect storm: unraveling the interplay of genetic predisposition and viral triggers in type 1 diabetes pathogenesis.Frontiers in endocrinology · 2025Review
- TGF-β-mediated crosstalk between TIGITNature communications · 2024Article
- Revisiting T-cell adhesion molecules as potential targets for cancer immunotherapy: CD226 and CD2.Experimental & molecular medicine · 2024Review
- Advancing Animal Models of Human Type 1 Diabetes.Cold Spring Harbor perspectives in medicine · 2024Review
- Inhibition of CD226 Co-Stimulation Suppresses Diabetes Development in the NOD Mouse by Augmenting Tregs and Diminishing Effector T Cell Function.bioRxiv : the preprint server for biology · 2024Article
- PPARs at the crossroads of T cell differentiation and type 1 diabetes.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Costimulation serves as a critical checkpoint for T-cell activation, and several genetic variants affecting costimulatory pathways confer risk for autoimmune diseases. A single nucleotide polymorphism (rs763361) in the CD226 gene encoding a costimulatory receptor increases susceptibility to multiple autoimmune diseases, including type 1 diabetes. We previously found that Cd226 knockout protected NOD mice from disease, but the impact of CD226 on individual immune subsets remained unclear. Our prior reports implicate regulatory T cells (Tregs), as human CD226+ Tregs exhibit reduced suppressive function. Hence, we hypothesized that genomic Cd226 gene deletion would increase Treg stability and that Treg-specific Cd226 deletion would inhibit diabetes in NOD mice. Indeed, crossing NOD.Cd226-/- and a NOD Treg-lineage tracing strain resulted in decreased pancreatic Foxp3-deficient "ex-Tregs." We generated a novel Treg-conditional knockout (TregΔCd226) strain that displayed decreased insulitis and diabetes incidence. CD226-deficient pancreatic Tregs had increased expression of the coinhibitory counter-receptor T-cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT). Moreover, NOD splenocytes treated with TIGIT-Fc fusion protein exhibited reduced T-cell proliferation and interferon-γ production following anti-CD3/CD28 stimulation. This study demonstrates that a CD226/TIGIT imbalance contributes to Treg instability in NOD mice and highlights the potential for therapeutic targeting this costimulatory pathway to halt autoimmunity. ARTICLE HIGHLIGHTS:
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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.