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Peer-reviewedCC BY-NC-ND 4.0Proceedings of the National Academy of Sciences of the United States of America

Intrinsic function of leptin receptor–regulated endothelial PD-L1

  • Yiu Ming Cheung1,2
  • Hoi Wa Yeung1,2
  • Chufeng He1,2
  • Qile Zhang1,2
  • Chui Yiu Bamboo Chook1
  • Gary Tse3
  • Yun Liao4
  • Wing Tak Wong1,2
4 affiliations
  1. 1School of Life Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
  2. 2State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
  3. 3Department of Population Health, School of Nursing and Health Sciences, Hong Kong Metropolitan University, Hong Kong Special Administrative Region, China
  4. 4Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai 200080, China
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Abstract

Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein expressed in vascular endothelial cells (ECs). In contrast to cancer, our understanding of endothelial PD-L1 in relation to metabolic syndromes and its vascular complications is less studied. For example, its regulation and intrinsic function remain unclear. Here, we showed that endothelial PD-L1 is regulated by leptin receptor signaling in male mice. In particular, endothelial PD-L1 expression is affected by leptin resistance. A lack of leptin receptors leads to PD-L1 downregulation in vascular ECs via posttranslational degradation. To understand the fundamental roles of endothelial PD-L1, RNA interference and selective knockout are employed in human endothelium and animals, respectively. Silencing or deleting endothelial PD-L1 expression delays cell cycle progression and proliferation due to rat sarcoma (RAS)/mitogen-activated protein kinase (MAPK) inactivation. In obesity, endothelial PD-L1 deficiency impairs the EC turnover and worsens the vascular function. Overall, we provide an insight into how endothelial PD-L1 contributes to vascular homeostasis, suggesting its pathophysiological importance in maintaining cellular turnover.

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Cite

BibTeXRIS
BibTeX
@article{cheung2026intrinsic,
  title = {{Intrinsic function of leptin receptor–regulated endothelial PD-L1}},
  author = {Yiu Ming Cheung and Hoi Wa Yeung and Chufeng He and Qile Zhang and Chui Yiu Bamboo Chook and Gary Tse and Yun Liao and Wing Tak Wong},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  year = {2026},
  month = oct,
  doi = {10.1073/pnas.2609322123},
  url = {https://doi.org/10.1073/pnas.2609322123},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Intrinsic function of leptin receptor–regulated endothelial PD-L1
AU  - Yiu Ming Cheung
AU  - Hoi Wa Yeung
AU  - Chufeng He
AU  - Qile Zhang
AU  - Chui Yiu Bamboo Chook
AU  - Gary Tse
AU  - Yun Liao
AU  - Wing Tak Wong
PY  - 2026
DA  - 2026/10/29
JO  - Proceedings of the National Academy of Sciences of the United States of America
DO  - 10.1073/pnas.2609322123
UR  - https://doi.org/10.1073/pnas.2609322123
AB  - Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein expressed in vascular endothelial cells (ECs). In contrast to cancer, our understanding of endothelial PD-L1 in relation to metabolic syndromes and its vascular complications is less studied. For example, its regulation and intrinsic function remain unclear. Here, we showed that endothelial PD-L1 is regulated by leptin receptor signaling in male mice. In particular, endothelial PD-L1 expression is affected by leptin resistance. A lack of leptin receptors leads to PD-L1 downregulation in vascular ECs via posttranslational degradation. To understand the fundamental roles of endothelial PD-L1, RNA interference and selective knockout are employed in human endothelium and animals, respectively. Silencing or deleting endothelial PD-L1 expression delays cell cycle progression and proliferation due to rat sarcoma (RAS)/mitogen-activated protein kinase (MAPK) inactivation. In obesity, endothelial PD-L1 deficiency impairs the EC turnover and worsens the vascular function. Overall, we provide an insight into how endothelial PD-L1 contributes to vascular homeostasis, suggesting its pathophysiological importance in maintaining cellular turnover.
SN  - 0027-8424
SN  - 1091-6490
ER  -