The E3 ubiquitin ligase cullin 3 (Cul3) is critical for invariant NKT (iNKT) cell development, as iNKT cells lacking Cul3 accumulate in the immature developmental stages. However, the mechanisms by which Cul3 mediates iNKT cell development remain unknown. In this study, we investigated the role of Cul3 in both immature and mature thymic iNKT cells using a mouse model with a T cell-specific deletion of Cul3. We found that mature iNKT cells lacking Cul3 proliferated and died more than wild-type cells did. These cells also displayed increased glucose metabolism and autophagy. Interestingly, we found that tight regulation of iron homeostasis is critical for iNKT cell development. Without Cul3, mature iNKT cells harbored higher levels of cytosolic iron, a phenotype associated with increased cell death. Taken together, our data suggest that Cul3 promotes iNKT cell development partially through intracellular iron homeostasis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10122431 | PMC |
| http://dx.doi.org/10.4049/immunohorizons.2300002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
AXL: shapers of tumor progression and immunosuppressive microenvironments.
Mol Cancer
January 2025
Department of Respiratory Disease, Daping Hospital, Army Medical University, Chongqing, 400042, China.
As research progresses, our understanding of the tumor microenvironment (TME) has undergone profound changes. The TME evolves with the developmental stages of cancer and the implementation of therapeutic interventions, transitioning from an immune-promoting to an immunosuppressive microenvironment. Consequently, we focus intently on the significant role of the TME in tumor proliferation, metastasis, and the development of drug resistance.
View Article and Find Full Text PDFEngineered Cellular Therapies for the Treatment of Thoracic Cancers.
Cancers (Basel)
December 2024
Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Thoracic malignancies (lung cancers and malignant pleural mesothelioma) are prevalent worldwide and are associated with high morbidity and mortality. Effective treatments are needed for patients with advanced disease. Cell therapies are a promising approach to the treatment of advanced cancers that make use of immune effector cells that have the ability to mediate antitumor immune responses.
View Article and Find Full Text PDFNeutrophil and Colorectal Cancer.
Int J Mol Sci
December 2024
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Colorectal cancer (CRC) is often associated with metastasis and recurrence and is the leading cause of cancer-related mortality. In the progression of CRC, recent studies have highlighted the critical role of neutrophils, particularly tumor-associated neutrophils (TANs). TANs have both tumor-promoting and tumor-suppressing activities, contributing to metastasis, immunosuppression, angiogenesis, and epithelial-to-mesenchymal transition.
View Article and Find Full Text PDFSUGT1 is a prognostic biomarker and is associated with immune infiltrates in ovarian cancer.
Eur J Med Res
January 2025
Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, NO. 3 Qingchun East Road, Hangzhou, 310016, China.
Background: Ovarian cancer (OC) is a prevalent gynecological malignancy with a relatively dismal prognosis. The SGT1 homolog (SUGT1) protein, which interacts with heat shock protein 90 and is essential for the G1/S and G2/M transitions, was formerly thought to be a cancer promoter, but its precise role in OC remains unknown.
Methods: We conducted a comprehensive bioinformatics analysis of SUGT1 expression in patients with OC compared with their normal controls, including the data from the cancer genome atlas (TCGA), genotype-tissue expression (GTEx) databases, gene ontology (GO) analysis, Kyoto Encylopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analysis (GSEA), single sample gene set enrichment analysis (ssGSEA).
CD70-targeted iPSC-derived CAR-NK cells display potent function against tumors and alloreactive T cells.
Cell Rep Med
December 2024
Bone Marrow Transplantation Center of the First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou 311121, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou 310058, China. Electronic address:
Clinical application of autologous chimeric antigen receptor (CAR)-T cells is complicated by limited targeting of cancer types, as well as the time-consuming and costly manufacturing process. We develop CD70-targeted, induced pluripotent stem cell-derived CAR-natural killer (NK) (70CAR-iNK) cells as an approach for universal immune cell therapy. Besides the CD70-targeted CAR molecule, 70CAR-iNK cells are modified with CD70 gene knockout, a high-affinity non-cleavable CD16 (hnCD16), and an interleukin (IL)-15 receptor α/IL-15 fusion protein (IL15RF).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!