ArticleThe Journal of clinical investigation2022
The FoxO4/DKK3 axis represses IFN-γ expression by Th1 cells and limits antimicrobial immunity.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Pooled it
- Review
- The "cytokine storm" in infection and sepsis: win the battle but lose the war.Military Medical Research · 2026Review
- Abnormal Elevation of the Expression of Costimulatory Molecule CD226 in Graves' DiseaseEndocrine, metabolic & immune disorders drug targets · 2026Article
- Recent advances in infections as risk factors for lymphoma: a review of the effects of viral, bacterial, and fungal infections in lymphoma.Archives of microbiology · 2025Review
- Plasma Exosomes Derived from Patients with Primary Immune Thrombocytopenia Attenuate TBX21Inflammation · 2025Article
- Unraveling the genetic diversity and adaptive traits of laboratory pig breeds within the perspective of whole - genome resequencing.BMC genomics · 2025Article
- Targeting DKK3 to remodel tumor immune microenvironment and enhance cancer immunotherapy.BMC cancer · 2025Article
- FOXO4-SP6 axis controls surface epithelium commitment by mediating epigenomic remodeling.Stem cell reports · 2025Article
- Integrative Bioinformatic Analysis of Cellular Senescence Genes in Ovarian Cancer: Molecular Subtyping, Prognostic Risk Stratification, and Chemoresistance Prediction.Biomedicines · 2025Article
- Reduced circulating regulatory T cells in primary Sjögren's syndrome: the contribution of enhanced apoptosis and impaired survival.Frontiers in immunology · 2025Article
- Pseudokinase STK40 promotes TScience advances · 2024Article
- Forkhead Box O (FOXO) signaling in NSCLC: pathways to targeted therapies.EXCLI journal · 2024Article
- Dormant tumors circumvent tumor-specific adaptive immunity by establishing a Treg-dominated niche via DKK3.JCI insight · 2023Article
- Inhibition of DYRK1B suppresses inflammation in allergic contact dermatitis model and Th1/Th17 immune response.Scientific reports · 2023Article
- Recombinant antigen P29 ofFrontiers in immunology · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Forkhead box O transcriptional factors, especially FoxO1 and FoxO3a, play critical roles in physiologic and pathologic immune responses. However, the function of FoxO4, another main member of the FoxO family, in lymphoid cells is still poorly understood. Here, we showed that loss of FoxO4 in T cells augmented IFN-γ production of Th1 cells in vitro. Correspondingly, conditional deletion of FoxO4 in CD4+ T cells enhanced T cell-specific responses to Listeria monocytogenes infection in vivo. Genome-wide occupancy and transcriptomic analyses identified Dkk3 (encoding the Dickkopf-3 protein) as a direct transcriptional target of FoxO4. Consistent with the FoxO4-DKK3 relationship, recombinant DKK3 protein restored normal levels of IFN-γ production in FoxO4-deficient Th1 cells through the downregulation of lymphoid enhancer-binding factor 1 (Lef1) expression. Together, our data suggest a potential FoxO4/DKK3 axis in Th1 cell differentiation, providing what we believe to be an important insight and supplement for FoxO family proteins in T lymphocyte biology and revealing a promising target for the treatment of immune-related diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.