脂肪细胞OX40L促进肥胖患者的脂肪T细胞活化和胰岛素抵抗
Adipocyte OX40L promotes adipose T cell activation and insulin resistance in obesity.
摘要(中文译文)
T细胞在肥胖诱导的脂肪组织炎症和胰岛素抵抗中发挥关键作用，但调控其在脂肪组织中活化的共刺激信号仍不清楚。本研究系统分析了脂肪细胞和脂肪组织巨噬细胞中的共刺激分子，发现OX40配体（OX40L）是肥胖状态下上调最为显著的分子。OX40L在肥胖人群的脂肪细胞中同样升高。尽管巨噬细胞特异性敲除OX40L对代谢无影响，但全身性OX40缺失或脂肪细胞特异性敲除OX40L可减少内脏脂肪组织中Th1细胞的积聚，减轻炎症并改善胰岛素敏感性，且不影响脂肪含量。这些获益可被Th1细胞过继转移所逆转。使用中和抗体治疗性阻断OX40L可模拟基因敲除的保护效应。本研究揭示了脂肪细胞来源的OX40L是肥胖相关免疫功能障碍的关键介质，并确立其作为代谢性疾病组织特异性免疫治疗的可靶向检查点。
Abstract
T cells contribute critically to obesity-induced adipose inflammation and insulin resistance, yet the co-stimulatory signals that govern their activation in adipose tissue remain unclear. Here, we systematically profile co-stimulatory molecules in adipocytes and adipose tissue macrophages and identify OX40 ligand (OX40L) as the most robustly upregulated in obesity. OX40L is also elevated in adipocytes from obese humans. Although macrophage-specific OX40L deletion has no metabolic impact, global OX40 deficiency or adipocyte-specific OX40L deletion reduces Th1 cell accumulation in visceral adipose tissue, attenuates inflammation and improves insulin sensitivity without affecting adiposity. These benefits are reversed by Th1 cell transfer. Therapeutic blockade of OX40L with a neutralizing antibody mimics the protective effects of genetic deletion. Our findings identify adipocyte-derived OX40L as a critical mediator of obesity-associated immune dysfunction and establish it as a targetable checkpoint for tissue-specific immunotherapy in metabolic disease.
如何引用
AMA
Jianfeng Song, Qin Zeng, Yayi Jiao, Xiaoxiao Sun, Limin Xie, Jingpei Qiu, et al. Adipocyte OX40L promotes adipose T cell activation and insulin resistance in obesity.. Experimental & molecular medicine. 2026; doi:10.1038/s12276-026-01770-8.
APA
Jianfeng Song, Qin Zeng, Yayi Jiao, Xiaoxiao Sun, Limin Xie, Jingpei Qiu, et al (2026). Adipocyte OX40L promotes adipose T cell activation and insulin resistance in obesity.. Experimental & molecular medicine. https://doi.org/10.1038/s12276-026-01770-8
GB/T 7714
Jianfeng Song, Qin Zeng, Yayi Jiao, Xiaoxiao Sun, Limin Xie, Jingpei Qiu, et al. Adipocyte OX40L promotes adipose T cell activation and insulin resistance in obesity.[J]. Experimental & molecular medicine, 2026 doi:10.1038/s12276-026-01770-8.
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