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| Main Authors: | , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Cellular and molecular life sciences : CMLS
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40434714/ |
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| _version_ | 1868266198715596800 |
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| author | Liang, Wei Geng, Ming Rao, Wenzhuo Li, Kang Zhu, Yating Zheng, Yuying Wei, Xiumei Yang, Jialong |
| author_facet | Liang, Wei Geng, Ming Rao, Wenzhuo Li, Kang Zhu, Yating Zheng, Yuying Wei, Xiumei Yang, Jialong Liang, Wei Geng, Ming Rao, Wenzhuo Li, Kang Zhu, Yating Zheng, Yuying Wei, Xiumei Yang, Jialong |
| collection | PubMed - marine biology |
| contents | Dual phosphorylation of glycogen synthase kinase 3β differentially integrates metabolic programs to determine T cell immunity across vertebrates. Liang, Wei Geng, Ming Rao, Wenzhuo Li, Kang Zhu, Yating Zheng, Yuying Wei, Xiumei Yang, Jialong Animals Glycogen Synthase Kinase 3 beta Phosphorylation Mice Lymphocyte Activation Oxidative Phosphorylation Glycolysis T-Lymphocytes CD4-Positive T-Lymphocytes Cell Proliferation Mice, Inbred C57BL Signal Transduction CD8-Positive T-Lymphocytes Vertebrates The integration of metabolic programs with T cell signaling establishes a molecular foundation for immune metabolism. As a key metabolic regulator, GSK3β's activity is dynamically modulated by phosphorylation at Ser9 and Tyr216. However, the contribution of these phosphorylation sites on metabolism-driven T cell response remains unclear. Using tilapia and mouse models, we investigated the regulation of GSK3β on T cell metabolism and its evolutionary variation. In tilapia, T cell activation induces GSK3β signaling, linking to both glycolysis and oxidative phosphorylation (OXPHOS). Tyr216 phosphorylation preferentially promotes glycolysis, facilitating T cell activation, proliferation, and antibacterial immunity; while inhibition of Ser9 phosphorylation specifically enhances OXPHOS to sustain T cell responses. Differently, Tyr216 phosphorylation supports both glycolysis and OXPHOS in mouse, ensuring CD4 T and CD8 T cell activation, proliferation, and cytokine production. Although Ser9 phosphorylation controls OXPHOS, its inhibition impairs rather than enhances OXPHOS and CD4 T cell responses in mouse. We thus revealed a previously unknown mechanism underlying T cell metabolism and proposed that, through evolution, GSK3β has restructured the regulatory strategy, enabling bidirectional control of T cell metabolism and immunity in mammals and enhancing the flexibility of the adaptive immune system. |
| format | Artículo científico |
| id | pubmed_40434714 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Cellular and molecular life sciences : CMLS |
| record_format | pubmed |
| spellingShingle | Dual phosphorylation of glycogen synthase kinase 3β differentially integrates metabolic programs to determine T cell immunity across vertebrates. Liang, Wei Geng, Ming Rao, Wenzhuo Li, Kang Zhu, Yating Zheng, Yuying Wei, Xiumei Yang, Jialong Animals Glycogen Synthase Kinase 3 beta Phosphorylation Mice Lymphocyte Activation Oxidative Phosphorylation Glycolysis T-Lymphocytes CD4-Positive T-Lymphocytes Cell Proliferation Mice, Inbred C57BL Signal Transduction CD8-Positive T-Lymphocytes Vertebrates Dual phosphorylation of glycogen synthase kinase 3β differentially integrates metabolic programs to determine T cell immunity across vertebrates. Liang, Wei Geng, Ming Rao, Wenzhuo Li, Kang Zhu, Yating Zheng, Yuying Wei, Xiumei Yang, Jialong Animals Glycogen Synthase Kinase 3 beta Phosphorylation Mice Lymphocyte Activation Oxidative Phosphorylation Glycolysis T-Lymphocytes CD4-Positive T-Lymphocytes Cell Proliferation Mice, Inbred C57BL Signal Transduction CD8-Positive T-Lymphocytes Vertebrates The integration of metabolic programs with T cell signaling establishes a molecular foundation for immune metabolism. As a key metabolic regulator, GSK3β's activity is dynamically modulated by phosphorylation at Ser9 and Tyr216. However, the contribution of these phosphorylation sites on metabolism-driven T cell response remains unclear. Using tilapia and mouse models, we investigated the regulation of GSK3β on T cell metabolism and its evolutionary variation. In tilapia, T cell activation induces GSK3β signaling, linking to both glycolysis and oxidative phosphorylation (OXPHOS). Tyr216 phosphorylation preferentially promotes glycolysis, facilitating T cell activation, proliferation, and antibacterial immunity; while inhibition of Ser9 phosphorylation specifically enhances OXPHOS to sustain T cell responses. Differently, Tyr216 phosphorylation supports both glycolysis and OXPHOS in mouse, ensuring CD4 T and CD8 T cell activation, proliferation, and cytokine production. Although Ser9 phosphorylation controls OXPHOS, its inhibition impairs rather than enhances OXPHOS and CD4 T cell responses in mouse. We thus revealed a previously unknown mechanism underlying T cell metabolism and proposed that, through evolution, GSK3β has restructured the regulatory strategy, enabling bidirectional control of T cell metabolism and immunity in mammals and enhancing the flexibility of the adaptive immune system. |
| title | Dual phosphorylation of glycogen synthase kinase 3β differentially integrates metabolic programs to determine T cell immunity across vertebrates. |
| topic | Animals Glycogen Synthase Kinase 3 beta Phosphorylation Mice Lymphocyte Activation Oxidative Phosphorylation Glycolysis T-Lymphocytes CD4-Positive T-Lymphocytes Cell Proliferation Mice, Inbred C57BL Signal Transduction CD8-Positive T-Lymphocytes Vertebrates |
| url | https://pubmed.ncbi.nlm.nih.gov/40434714/ |