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| Main Authors: | , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
EMBO reports
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/41249580/ |
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Table of 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.