CTRP9 engages AdipoR1 and promotes T cell glycolysis and immunity.
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| Format: | Artículo científico |
| Sprache: | en |
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EMBO reports
2025
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| _version_ | 1868266125106610177 |
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| author | Li, Kunming Zhang, Jiansong Li, Kang Chen, Haokai Deng, Wenhai Rao, Wenzhuo Geng, Ming Zheng, Yuying Wei, Xiumei Yang, Jialong |
| author_facet | Li, Kunming Zhang, Jiansong Li, Kang Chen, Haokai Deng, Wenhai Rao, Wenzhuo Geng, Ming Zheng, Yuying Wei, Xiumei Yang, Jialong Li, Kunming Zhang, Jiansong Li, Kang Chen, Haokai Deng, Wenhai Rao, Wenzhuo Geng, Ming Zheng, Yuying Wei, Xiumei Yang, Jialong |
| collection | PubMed - marine biology |
| contents | CTRP9 engages AdipoR1 and promotes T cell glycolysis and immunity. Li, Kunming Zhang, Jiansong Li, Kang Chen, Haokai Deng, Wenhai Rao, Wenzhuo Geng, Ming Zheng, Yuying Wei, Xiumei Yang, Jialong Receptors, Adiponectin Animals Glycolysis Adiponectin T-Lymphocytes Mice Lymphocyte Activation Humans Signal Transduction Cell Proliferation Glycoproteins The adiponectin (ADPN) receptor (AdipoR) modulates T-cell responses, but its effects remain controversial since signaling can either promote or inhibit T-cell function. Interaction with the ligand ADPN inhibits T-cell responses, but given the existence of multiple AdipoR ligands, we hypothesize that ligand diversity underlies its differential effect in T-cell immunity. To test this, we use tilapia and mouse models. Tilapia encodes AdipoR1 but lacks ADPN. Instead, an alternative adipokine, CTRP9, engages AdipoR1. We find CTRP9-AdipoR1 interaction triggers Ca influx and activates the CaM-CaMKKβ-AMPK pathway, facilitating crosstalk with TCR signaling. This cascade enhances T-cell activation, proliferation, and antimicrobial immunity by promoting glycolysis. In mice, CTRP9 similarly enhances T-cell activation, proliferation, and cytokine production and improves the efficacy of anti-CD19 CAR-T cells in eliminating B-cell lymphoma in vitro. These findings reveal an evolutionarily conserved role of CTRP9 in promoting T-cell immunity, in contrast to the inhibitory effect exerted by ADPN. Mechanistically, CTRP9 and ADPN exert distinct effects on T-cell metabolism; CTRP9 enhances T-cell glycolysis, whereas ADPN suppresses it. We therefore propose ligand selectivity as a determinant of AdipoR1-dependent T-cell immune outcomes. |
| format | Artículo científico |
| id | pubmed_41249580 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | EMBO reports |
| record_format | pubmed |
| spellingShingle | CTRP9 engages AdipoR1 and promotes T cell glycolysis and immunity. Li, Kunming Zhang, Jiansong Li, Kang Chen, Haokai Deng, Wenhai Rao, Wenzhuo Geng, Ming Zheng, Yuying Wei, Xiumei Yang, Jialong Receptors, Adiponectin Animals Glycolysis Adiponectin T-Lymphocytes Mice Lymphocyte Activation Humans Signal Transduction Cell Proliferation Glycoproteins CTRP9 engages AdipoR1 and promotes T cell glycolysis and immunity. Li, Kunming Zhang, Jiansong Li, Kang Chen, Haokai Deng, Wenhai Rao, Wenzhuo Geng, Ming Zheng, Yuying Wei, Xiumei Yang, Jialong Receptors, Adiponectin Animals Glycolysis Adiponectin T-Lymphocytes Mice Lymphocyte Activation Humans Signal Transduction Cell Proliferation Glycoproteins The adiponectin (ADPN) receptor (AdipoR) modulates T-cell responses, but its effects remain controversial since signaling can either promote or inhibit T-cell function. Interaction with the ligand ADPN inhibits T-cell responses, but given the existence of multiple AdipoR ligands, we hypothesize that ligand diversity underlies its differential effect in T-cell immunity. To test this, we use tilapia and mouse models. Tilapia encodes AdipoR1 but lacks ADPN. Instead, an alternative adipokine, CTRP9, engages AdipoR1. We find CTRP9-AdipoR1 interaction triggers Ca influx and activates the CaM-CaMKKβ-AMPK pathway, facilitating crosstalk with TCR signaling. This cascade enhances T-cell activation, proliferation, and antimicrobial immunity by promoting glycolysis. In mice, CTRP9 similarly enhances T-cell activation, proliferation, and cytokine production and improves the efficacy of anti-CD19 CAR-T cells in eliminating B-cell lymphoma in vitro. These findings reveal an evolutionarily conserved role of CTRP9 in promoting T-cell immunity, in contrast to the inhibitory effect exerted by ADPN. Mechanistically, CTRP9 and ADPN exert distinct effects on T-cell metabolism; CTRP9 enhances T-cell glycolysis, whereas ADPN suppresses it. We therefore propose ligand selectivity as a determinant of AdipoR1-dependent T-cell immune outcomes. |
| title | CTRP9 engages AdipoR1 and promotes T cell glycolysis and immunity. |
| topic | Receptors, Adiponectin Animals Glycolysis Adiponectin T-Lymphocytes Mice Lymphocyte Activation Humans Signal Transduction Cell Proliferation Glycoproteins |
| url | https://pubmed.ncbi.nlm.nih.gov/41249580/ |