Authors
Jianfeng Song, Qin Zeng, Yayi Jiao, Xiaoxiao Sun, Limin Xie, Jingpei Qiu, Yujin Ding, Wanyu Hu, Fanqi Wang, Biling Huang, Wuqian Mai, Ying Mei, Dandan Wang, Lan Xie, Xiang Xiao, Wei Liu, Willa A Hsueh, Xian C Li, Tuo Deng
Published in
Experimental & molecular medicine. Jul 06, 2026. Epub Jul 06, 2026.
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.
PMID:
42409961
Bibliographic data and abstract were imported from PubMed on 07 Jul 2026.
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