NAD ⁺ metabolic restoration resolves the inflammation-immunocompetence trade-off in lung graft-versus-host disease
8 affiliations
- 1Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Centre of Soochow University, Suzhou 215001, China.
- 2Organoid Innovation Center, Suzhou Institute of Nanotech and Nano-bionics, Chinese Academy of Sciences, Suzhou 215123, China.
- 3School of Nano-Technology and Nano-Bionics, University of Science and Technology of China, Hefei 230026, China.
- 4National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215000, China.
- 5Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215000, China.
- 6Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
- 7Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300000, China.
- 8Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Abstract
Chronic lung graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains difficult to treat, and broad immunosuppression increases infection risk. Single-cell profiling of bronchoalveolar lavage from bronchiolitis obliterans lesions revealed collapse of an epithelial nicotinamide adenine dinucleotide (NAD⁺) metabolic axis with pathogenic immune-epithelial remodeling, nominating NAD⁺ restoration as an entry point. Because free NAD⁺ is poorly cell-permeable and rapidly consumed, we engineered CaNAD⁺-PGB-LiP (CNAPL), a high-payload NAD⁺ nanomedicine enabling direct intracellular replenishment. In murine allo-HSCT GVHD, CNAPL improved clinical scores and survival, reduced vascular and epithelial injury, and curtailed hyperinflammation and effector overactivation across GVHD target organs. Unlike immunosuppression, CNAPL preserved phagocytosis, NK/NKT cell (natural killer/natural killer T cell) cytotoxicity, and T cell memory. In posttransplant influenza or Klebsiella infection, CNAPL maintained pathogen control without rekindling GVHD, decoupling inflammation control from infection susceptibility. This metabolism-centered, host-directed strategy restores immune-tissue homeostasis and provides a practical translational path for durable lung GVHD control with preserved antimicrobial defense.
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BibTeX
@article{li2026metabolic,
title = {{NAD ⁺ metabolic restoration resolves the inflammation-immunocompetence trade-off in lung graft-versus-host disease}},
author = {Jing Li and Zheng Zhou and Jiaqian Qi and Fan Zhang and Ziyan Zhang and Xueqian Li and Shuhui Jiang and Xiang Li and Luyao Wang and Xiahong Xie and Jinfeng Chen and Kanghua Zeng and Yue Han and Junhong Jiang and Mingzhou Ye},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.aef3338},
url = {https://www.science.org/doi/10.1126/sciadv.aef3338},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - NAD ⁺ metabolic restoration resolves the inflammation-immunocompetence trade-off in lung graft-versus-host disease
AU - Jing Li
AU - Zheng Zhou
AU - Jiaqian Qi
AU - Fan Zhang
AU - Ziyan Zhang
AU - Xueqian Li
AU - Shuhui Jiang
AU - Xiang Li
AU - Luyao Wang
AU - Xiahong Xie
AU - Jinfeng Chen
AU - Kanghua Zeng
AU - Yue Han
AU - Junhong Jiang
AU - Mingzhou Ye
PY - 2026
DA - 2026/10/23
JO - Science Advances
DO - 10.1126/sciadv.aef3338
UR - https://www.science.org/doi/10.1126/sciadv.aef3338
AB - Chronic lung graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains difficult to treat, and broad immunosuppression increases infection risk. Single-cell profiling of bronchoalveolar lavage from bronchiolitis obliterans lesions revealed collapse of an epithelial nicotinamide adenine dinucleotide (NAD⁺) metabolic axis with pathogenic immune-epithelial remodeling, nominating NAD⁺ restoration as an entry point. Because free NAD⁺ is poorly cell-permeable and rapidly consumed, we engineered CaNAD⁺-PGB-LiP (CNAPL), a high-payload NAD⁺ nanomedicine enabling direct intracellular replenishment. In murine allo-HSCT GVHD, CNAPL improved clinical scores and survival, reduced vascular and epithelial injury, and curtailed hyperinflammation and effector overactivation across GVHD target organs. Unlike immunosuppression, CNAPL preserved phagocytosis, NK/NKT cell (natural killer/natural killer T cell) cytotoxicity, and T cell memory. In posttransplant influenza or Klebsiella infection, CNAPL maintained pathogen control without rekindling GVHD, decoupling inflammation control from infection susceptibility. This metabolism-centered, host-directed strategy restores immune-tissue homeostasis and provides a practical translational path for durable lung GVHD control with preserved antimicrobial defense.
SN - 2375-2548
ER -