| 2018 |
WDFY4, a BEACH domain-containing protein, is essential for cross-presentation of cell-associated antigens by Batf3-dependent cDC1s (CD8α+/XCR1+ classical dendritic cells) to CD8+ T cells in mice, identified via a functional CRISPR screen. WDFY4 knockout mice fail to prime virus-specific CD8+ T cells in vivo and cannot induce tumor rejection, but retain normal cDC1 populations, MHC-II presentation, and IL-12 production, demonstrating a specific role in the cross-presentation pathway rather than cDC1 development. |
CRISPR screen, Wdfy4-/- mouse knockout, in vivo CD8+ T cell priming assays, tumor rejection assays, flow cytometry, Toxoplasma infection model |
Science (New York, N.Y.) |
High |
30409884
|
| 2025 |
WDFY4-dependent cross-presentation is not exclusive to cDC1s; cDC2s also use a WDFY4-dependent pathway to cross-present immune complex antigens to CD8+ T cells in vivo, enabling tumor rejection even in the absence of cDC1s. Monocyte-derived DCs do not participate in this WDFY4-dependent cross-presentation. |
Genetic mouse models (cDC1-deficient, cDC2-deficient, Wdfy4-/- mice), immune complex vaccination, in vivo CD8+ T cell priming, tumor rejection assays |
The Journal of experimental medicine |
High |
39918736
|
| 2018 |
Both full-length WDFY4 and a truncated isoform (tr-WDFY4) physically interact with pattern recognition receptors TLR3, TLR4, TLR9, and MDA5, and augment NF-κB activation downstream of these receptors. The truncated isoform (encoded by the CADM-risk allele) also enhances MDA5-induced apoptosis more than full-length WDFY4. |
Co-immunoprecipitation (interaction with TLRs and MDA5), NF-κB reporter assays, apoptosis assays, trans-eQTL analysis |
Annals of the rheumatic diseases |
Medium |
29331962
|
| 2018 |
In B cells, WDFY4 facilitates noncanonical autophagic activity. Loss of WDFY4 in B cells (conditional knockout) increases LC3 lipidation independently of p62 and Beclin1 (canonical autophagy markers), and leads to defects in B cell development (pro- to pre-B cell transition), reduced peripheral B cell numbers, impaired antibody responses, and amelioration of SLE phenotypes including autoantibody production and glomerulonephritis. |
B cell-conditional Wdfy4 knockout mice, LC3 lipidation assay, flow cytometry of B cell subsets, pristane-induced SLE model, antibody response assays |
Journal of immunology (Baltimore, Md. : 1950) |
Medium |
30257884
|
| 2023 |
In NOD mice, WDFY4 deficiency (via CRISPR/Cas9) abolishes cross-presentation of cell-associated antigens by cDC1s, preventing priming of autoreactive CD8+ T cells, and as a consequence blocks recruitment of autoreactive CD4+ T cells into islets and prevents autoimmune diabetes, while MHC-II antigen presentation and CD4+ T cell activation in lymph nodes remain intact. |
CRISPR/Cas9 Wdfy4-/- NOD mice, cross-presentation assays, diabetes incidence monitoring, insulitis histology, T cell priming assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
36940342
|
| 2021 |
Selective deficiency of WDFY4 in T cells leads to reduced CD8+ T cell numbers in the periphery, enhanced CD8+ T cell apoptosis, elevated intracellular reactive oxygen species (ROS) with upregulation of Nox2, and activation of the p53 pathway with inhibition of the ERK pathway. This results in impaired antitumor CD8+ T cell responses. |
T cell-conditional Wdfy4 knockout mice, flow cytometry, ROS measurement, apoptosis assays, p53/ERK pathway analysis, transplantable tumor model |
Molecular immunology |
Medium |
34482201
|
| 2021 |
WDFY4 deficiency in mice promotes Th2 cell differentiation and Th2 cytokine production in vitro and in vivo, and exacerbates ovalbumin-induced asthma with enhanced inflammatory cell infiltration, goblet cell hyperplasia, mucus production, and collagen deposition. |
Wdfy4-/- mouse model, in vitro Th2 differentiation from naïve CD4+ T cells, OVA-induced asthma model, cytokine measurement, histology |
International archives of allergy and immunology |
Medium |
34425575
|
| 2025 |
WDFY4 interacts with lysosomal transmembrane protein LAPTM5, validated by co-immunoprecipitation and immunofluorescence co-localization, and this interaction promotes ferroptosis in endothelial cells. Mechanistically, WDFY4 promotes LAPTM5 expression, which suppresses the CDC42/mTOR/4EBP1/SLC7A11 pathway to enhance ferroptosis. Endothelial-specific WDFY4 knockout reduces atherosclerotic plaque formation in ApoE-/- mice. |
Co-immunoprecipitation, immunofluorescence co-localization, WDFY4 knockdown/knockout in vitro and in vivo (endothelium-specific transgenic mice), ApoE-/- HFD atherosclerosis model, pathway inhibitor rescue experiments |
Journal of cellular and molecular medicine |
Medium |
40755163
|
| 2012 |
The transcription factor YY1 (Yinyang1) binds to an intronic SLE-associated variant site (rs877819) in WDFY4; the risk allele (A) reduces YY1 binding affinity, resulting in lower transcriptional activity of WDFY4. WDFY4 is significantly downregulated in SLE patients carrying this allele. |
Electrophoretic mobility shift assay (EMSA), supershift assay, dual-luciferase reporter assay, YY1 siRNA knockdown and overexpression, chromatin immunoprecipitation (ChIP), allelic expression analysis |
Genes and immunity |
Medium |
22972472
|