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Autophagy-mediated TET2 degradation by ALV-J Env protein suppresses innate immune activation to promote viral replication.
J Virol
January 2025
College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China.
Unlabelled: Avian leukosis virus subgroup J (ALV-J) poses a significant threat to the poultry industry; yet, our understanding of its replication and pathogenic mechanisms is limited. The Ten-Eleven Translocation 2 (TET2) is an indispensable regulatory factor in active DNA demethylation and immune response regulation. This study reports a significant and time-dependent decrease in TET2 levels following ALV-J infection and shows that the reduction of TET2 protein is mediated by the autophagy pathway.
View Article and Find Full Text PDFDeficiency of TET2-mediated KMT2D self-transcription confers a targetable vulnerability in hepatocellular carcinoma.
PNAS Nexus
November 2024
Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China.
Article Synopsis
- Hepatocellular carcinoma (HCC) is a major cause of cancer deaths globally, and traditional treatments often worsen patient conditions, highlighting the need for new management strategies.
- Research shows that TET2 and KMT2D work together to regulate important genes involved in HCC, which could be targeted for therapy; KMT2D is particularly important as a tumor suppressor and enhances the anti-cancer effects of vitamin C.
- The study reveals that patients with higher levels of TET2 and KMT2D have better outcomes, suggesting that these proteins play a critical role in HCC progression and could be used as potential targets for treatment.
Tet2 modulates M2 macrophage polarization via mRNA 5-methylcytosine in allergic rhinitis.
Int Immunopharmacol
December 2024
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address:
Background: Allergic rhinitis (AR) represents a hallmark of obvious hypersensitivity with an imbalance of immune responses, including abnormal macrophage activity in local tissues. It has been reported that alternatively activated macrophages (M2) may contribute to allergic pathogenesis. Ten-eleven translocation (Tet) enzymes can oxidize 5-methylcytosine (m5C) in mRNA, implying the epigenetic regulation of post-transcriptional RNA modification.
View Article and Find Full Text PDFAscorbate deficiency increases quiescence and self-renewal in hematopoietic stem cells and multipotent progenitors.
Blood
January 2025
Department of Pediatrics, Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX.
Article Synopsis
- Ascorbate (vitamin C) decreases the function of hematopoietic stem cells (HSCs) and helps prevent leukemia by enhancing the activity of the Tet2 tumor suppressor.
- Deleting the Slc23a2 transporter from hematopoietic cells caused a significant drop in ascorbate levels within HSCs and multipotent progenitors (MPPs) but did not affect overall plasma ascorbate levels.
- This deficiency led to increased reconstitution and self-renewal capabilities of HSCs and MPPs when transplanted into irradiated mice, particularly in their quiescent states, indicating that low ascorbate levels may enhance their long-term potential.
Epigenetic regulators of clonal hematopoiesis control CD8 T cell stemness during immunotherapy.
Science
October 2024
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Epigenetic reinforcement of T cell exhaustion is known to be a major barrier limiting T cell responses during immunotherapy. However, the core epigenetic regulators restricting antitumor immunity during prolonged antigen exposure are not clear. We investigated three commonly mutated epigenetic regulators that promote clonal hematopoiesis to determine whether they affect T cell stemness and response to checkpoint blockade immunotherapy.
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