ArticleProceedings of the National Academy of Sciences of the United States of America2021
DNAM-1 regulates Foxp3 expression in regulatory T cells by interfering with TIGIT under inflammatory conditions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- Specific depletion of TIGITJournal for immunotherapy of cancer · 2026Article
- Targeting regulatory T cells in glioblastoma: from mechanistic insights to novel immunotherapeutic strategies.Frontiers in immunology · 2026Review
- Imbalance of stem-like and effector T cell states in children with early type 1 diabetes across conventional and regulatory subsets.Nature communications · 2025Article
- A co-stimulatory signal via the coinhibitory TIGIT.Nature immunology · 2025Article
- αTIGIT-IL2 achieves tumor regression by promoting tumor-infiltrating regulatory T cell fragility in mouse models.Nature communications · 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
- Immunotherapy with low-dose IL-2 attenuates vascular injury in mice with diabetic and neovascular retinopathy by restoring the balance between Foxp3Diabetologia · 2025Article
- TIGIT Regulates T Cell Inflammation in Airway Inflammatory Diseases.Inflammation · 2025Review
- Tiragolumab and TIGIT: pioneering the next era of cancer immunotherapy.Frontiers in pharmacology · 2025Review
- 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
- Tumor Microenvironment Drives the Cross-Talk Between Co-Stimulatory and Inhibitory Molecules in Tumor-Infiltrating Lymphocytes: Implications for Optimizing Immunotherapy Outcomes.International journal of molecular sciences · 2024Review
- Dysfunction of type 1 and type 2 immune cells: a lesson from exhausted-like ILC2s and their activation-induced cell death.International immunology · 2024Review
- Revisiting T-cell adhesion molecules as potential targets for cancer immunotherapy: CD226 and CD2.Experimental & molecular medicine · 2024Review
- TIGIT reverses IFN-α-promoted Th1-like Tregs via in-sequence effects dependent on STAT4.Arthritis research & therapy · 2023Article
- Treg-Specific CD226 Deletion Reduces Diabetes Incidence in NOD Mice by Improving Regulatory T-Cell Stability.Diabetes · 2023Article
- TIGIT mediates activation-induced cell death of ILC2s during chronic airway allergy.The Journal of experimental medicine · 2023Article
- Mechanisms regulating the loss of Tregs in HUPO mice that develop spontaneous inflammatory arthritis.iScience · 2023Article
- Anti-human-TIGIT agonistic antibody ameliorates autoimmune diseases by inhibiting Tfh and Tph cells and enhancing Treg cells.Communications biology · 2023Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulatory T (Treg) cells that express forkhead box P3 (Foxp3) are pivotal for immune tolerance. Although inflammatory mediators cause Foxp3 instability and Treg cell dysfunction, their regulatory mechanisms remain incompletely understood. Here, we show that the transfer of Treg cells deficient in the activating immunoreceptor DNAM-1 ameliorated the development of graft-versus-host disease better than did wild-type Treg cells. We found that DNAM-1 competes with T cell immunoreceptor with Ig and ITIM domains (TIGIT) in binding to their common ligand CD155 and therefore regulates TIGIT signaling to down-regulate Treg cell function without DNAM-1-mediated intracellular signaling. DNAM-1 deficiency augments TIGIT signaling; this subsequently inhibits activation of the protein kinase B-mammalian target of rapamycin complex 1 pathway, resulting in the maintenance of Foxp3 expression and Treg cell function under inflammatory conditions. These findings demonstrate that DNAM-1 regulates Treg cell function via TIGIT signaling and thus, it is a potential molecular target for augmenting Treg function in inflammatory diseases.
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