ArticleProceedings of the National Academy of Sciences of the United States of America2012
Dickkopf-3, an immune modulator in peripheral CD8 T-cell tolerance.
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 32 papers, 1 of them a synthesis that pooled it.
What it found
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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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Pooled it
- DKK3 Initially Preserves Acinar Integrity Through MEK-Fos Signaling, but Later Switches to an Oncogenic Role in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Urinary Dickkopf-Related Protein 3-A Potential Long-Term Biomarker for Progressive CKD in Children.Kidney international reports · 2025Article
- Polyfunctional CD8Molecular oncology · 2025Article
- Overexpressed Wnt-7a acts as a potential antitumor immune modulator and predicts poor prognosis in HNSCC.Heliyon · 2025Article
- Redefinition of Synovial Fibroblasts in Rheumatoid Arthritis.Aging and disease · 2024Review
- The Multifaceted Role of Human Dickkopf-3 (DKK-3) in Development, Immune Modulation and Cancer.Cells · 2023Review
- Dormant tumors circumvent tumor-specific adaptive immunity by establishing a Treg-dominated niche via DKK3.JCI insight · 2023Article
- DKK3 expression is associated with immunosuppression and poor prognosis in glioblastoma, in contrast to lower-grade gliomas.BMC neurology · 2023Article
- Multiomics of Colorectal Cancer Organoids Reveals Putative Mediators of Cancer Progression Resulting from SMAD4 Inactivation.Journal of proteome research · 2023Article
- High DKK3 expression related to immunosuppression was associated with poor prognosis in glioblastoma: machine learning approach.Cancer immunology, immunotherapy : CII · 2022Article
- A Fresh Glimpse into Cartilage Immune Privilege.Cartilage · 2022Review
- Review
- The FoxO4/DKK3 axis represses IFN-γ expression by Th1 cells and limits antimicrobial immunity.The Journal of clinical investigation · 2022Article
- Dickkopf proteins in pathological inflammatory diseases.Journal of leukocyte biology · 2022Review
- Dickkopf 3: a Novel Target Gene of miR-25-3p in Promoting Fibrosis-Related Gene Expression in Myocardial Fibrosis.Journal of cardiovascular translational research · 2021Article
- Dickkopf-related protein 3 alters aerobic glycolysis in pancreatic cancer BxPC-3 cells, promoting CD4European journal of medical research · 2021Article
- From thymus to periphery: Molecular basis of effector γδ-T cell differentiation.Immunological reviews · 2020Review
- Dickkopf-3: Current Knowledge in Kidney Diseases.Frontiers in physiology · 2020Review
- Macrophages as an Emerging Source of Wnt Ligands: Relevance in Mucosal Integrity.Frontiers in immunology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In healthy individuals, T cells react against incoming pathogens, but remain tolerant to self-antigens, thereby preventing autoimmune reactions. CD4 regulatory T cells are major contributors in induction and maintenance of peripheral tolerance, but a regulatory role has been also reported for several subsets of CD8 T cells. To determine the molecular basis of peripheral CD8 T-cell tolerance, we exploited a double transgenic mouse model in which CD8 T cells are neonatally tolerized following interaction with a parenchymal self-antigen. These tolerant CD8 T cells have regulatory capacity and can suppress T cells in an antigen-specific manner during adulthood. Dickkopf-3 (DKK3) was found to be expressed in the tolerant CD8 T cells and to be essential for the observed CD8 T-cell tolerance. In vitro, genetic deletion of DKK3 or blocking with antibodies restored CD8 T-cell proliferation and IL-2 production in response to the tolerizing self-antigen. Moreover, exogenous DKK3 reduced CD8 T-cell reactivity. In vivo, abrogation of DKK3 function reversed tolerance, leading to eradication of tumors expressing the target antigen and to rejection of autologous skin grafts. Thus, our findings define DKK3 as a immune modulator with a crucial role for CD8 T-cell tolerance.
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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.