ArticleFrontiers in immunology2015
Dickkopf-3, a tissue-derived modulator of local T-cell responses.
Article in Frontiers in immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- Comprehensive Meta-Analysis of Differentially Expressed Proteins in Cerebrospinal Fluid Associated with Multiple Sclerosis.International journal of molecular sciences · 2025Pooled it
- Pooled it
- Ad-SGE-DKK3 Gene Therapy Overcomes Resistance to Immune Checkpoint Blockade in Pleural Mesothelioma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- 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
- Urinary Dickkopf 3 Is Not an Independent Risk Factor in a Cohort of Kidney Transplant Recipients and Living Donors.International journal of molecular sciences · 2024Article
- Assessment and Risk Prediction of Chronic Kidney Disease and Kidney Fibrosis Using Non-Invasive Biomarkers.International journal of molecular sciences · 2024Review
- Article
- DKK3 as a potential novel biomarker in patients with autosomal polycystic kidney disease.Clinical kidney journal · 2024Article
- 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
- Pan-cancer T cell atlas links a cellular stress response state to immunotherapy resistance.Nature medicine · 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
- A novel ΔNp63-dependent immune mechanism improves prognosis of HPV-related head and neck cancer.Frontiers in immunology · 2023Article
- High DKK3 expression related to immunosuppression was associated with poor prognosis in glioblastoma: machine learning approach.Cancer immunology, immunotherapy : CII · 2022Article
- 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 Proteins and Their Role in Cancer: A Family of Wnt Antagonists with a Dual Role.Pharmaceuticals (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adaptive immune system protects organisms from harmful environmental insults. In parallel, regulatory mechanisms control immune responses in order to assure preservation of organ integrity. Yet, molecules involved in the control of T-cell responses in peripheral tissues are poorly characterized. Here, we investigated the function of Dickkopf-3 in the modulation of local T-cell reactivity. Dkk3 is a secreted, mainly tissue-derived protein with highest expression in organs considered as immune-privileged such as the eye, embryo, placenta, and brain. While T-cell development and activation status in naïve Dkk3-deficient mice was comparable to littermate controls, we found that Dkk3 contributes to the immunosuppressive microenvironment that protects transplanted, class-I mismatched embryoid bodies from T-cell-mediated rejection. Moreover, genetic deletion or antibody-mediated neutralization of Dkk3 led to an exacerbated experimental autoimmune encephalomyelitis (EAE). This phenotype was accompanied by a change of T-cell polarization displayed by an increase of IFNγ-producing T cells within the central nervous system. In the wild-type situation, Dkk3 expression in the brain was up-regulated during the course of EAE in an IFNγ-dependent manner. In turn, Dkk3 decreased IFNγ activity and served as part of a negative feedback mechanism. Thus, our findings suggest that Dkk3 functions as a tissue-derived modulator of local CD4(+) and CD8(+) T-cell responses.
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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 OpenQuestion graph.