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Research ArticleImmunologyInfectious diseaseInflammation
Open Access | 
10.1172/jci.insight.197224
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Di, L. in: PubMed | Google Scholar
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Fan, J. in: PubMed | Google Scholar
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Wang, R. in: PubMed | Google Scholar
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Li, Y. in: PubMed | Google Scholar
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
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1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Huang, S. in: PubMed | Google Scholar
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Nie, H. in: PubMed | Google Scholar
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Feng, X. in: PubMed | Google Scholar
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Zhang, H. in: PubMed | Google Scholar
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Du, J. in: PubMed | Google Scholar
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Huang, X. in: PubMed | Google Scholar
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Yu, A. in: PubMed | Google Scholar
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Xu, Z. in: PubMed | Google Scholar
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Xia, F. in: PubMed | Google Scholar
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Jiang, J. in: PubMed | Google Scholar
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Dai, S. in: PubMed | Google Scholar
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Xu, X. in: PubMed | Google Scholar
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Wang, Z. in: PubMed | Google Scholar
1Department of Trauma Medical Center, and
2Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, China.
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, China.
4Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China.
5Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
6Department of Emergency, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Address correspondence to: Ling Zeng, Department of Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: zengling_1025@tmmu.edu.cn. Or to: Zhen Wang, Department of Intensive Care Unit, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China, Email: dpicuwz@tmmu.edu.cn. Or to: Xiang Xu, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing 400042, China, Email: xiangxu@tmmu.edu.cn.
Find articles by Zeng, L. in: PubMed | Google Scholar
Published February 23, 2026 - More info
Published in Volume 11, Issue 4 on February 23, 2026
AbstractSepsis, a systemic inflammatory response to infection, remains a leading cause of mortality in intensive care units, with sepsis-induced immunosuppression being a critical pathophysiological process. In this study, we investigated the role of histone deacetylase 1 (HDAC1) in sepsis-induced CD8+ T cell exhaustion, a key driver of immunosuppression. Clinical analyses of patients with sepsis revealed that reduced peripheral blood lymphocyte levels, particularly CD8+ T cell depletion, strongly correlated with worsened outcomes. In a murine sepsis model, single-cell RNA-Seq revealed a significant decrease in the proportion of CD8+ T cells and an increase in the proportion of exhausted CD8+ T cells in mouse lungs. Adoptive transfer of CD8+ T cells effectively reduced sepsis mortality by preserving organ function. We further demonstrated that HDAC1 expression was significantly upregulated in CD8+ T cells from patients with sepsis. In vitro studies showed that HDAC1 inhibition preserved CD8+ T cell function by maintaining T cell activity and reducing the expression of inhibitory molecules such as PD-1. Pharmacological inhibition of HDAC1 reduced mortality and reversed CD8+ T cell exhaustion by restoring the balance between activator protein-1 (AP-1) and nuclear factor of activated T cells (NFAT). Additionally, we found that HDAC1 directly interacted with NFAT1, promoting its nuclear translocation and further enhancing the expression of inhibitory molecules. Our findings highlight HDAC1 as a potential therapeutic target for sepsis-induced immunosuppression. By elucidating the molecular mechanisms underlying HDAC1-mediated immunosuppression, we have provided potential strategies for developing immunomodulatory therapies for the treatment of sepsis.
Graphical Abstract
Introduction
Sepsis is a lethal, systemic multiorgan dysfunction caused by infection and resulting from an uncontrollable inflammatory response. Despite advances in intensive care, the mortality rates associated with sepsis and septic shock remain high. The in-hospital mortality rate of patients with sepsis is 10% to 20%. Septic shock, a subtype of sepsis that is characterized by severe cardiovascular abnormalities, has a 40% to 50% mortality rate (1). The immunopathology of sepsis is characterized by a biphasic response: initial hyperinflammation followed by profound immunosuppression. Although early innate immune clearance can restore homeostasis, persistent immune dysfunction contributes to secondary infections, which are now recognized as major drivers of sepsis-related death (2, 3). During sepsis-induced immunosuppression, macrophages are overactivated, DCs exhibit defects in antigen presentation or even undergo apoptosis, bone myeloid–derived suppressor cells (MDSCs) expand, and most lymphocytes except Tregs become dysfunctional and can even undergo cell death (4). These changes explain why therapeutic strategies aimed at blocking hyperinflammation, such as glucocorticoids or cytokine inhibitors, have largely failed in clinical trials (5, 6).
T lymphocytes, particularly CD8+ T cells, are central to adaptive immunity and play a pivotal role in pathogen clearance. Hotchkiss et al. reported extensive T cell death in the lungs and spleens of patients with sepsis and noted significant upregulation of inhibitory receptors, including PD-1, PD-L1, and CD25, on T cells (7, 8). The counts and ratios of CD4+ T cells and CD8+ T cells can serve as preliminary indicators for monitoring the immune status of patients with sepsis (9). Our prior work demonstrated increased TIM3 expression on CD4+ T cells and functional suppression mediated by HMGB1, but whether CD8+ T cells undergo similar regulatory changes remains unclear (6). Unlike infections such as malaria, where CD8+ T cell activation is enhanced (10), sepsis is associated with reduced CD8+ T cell counts and impaired cytotoxic function, which strongly correlates with secondary infections and mortality (11–13).
The imbalance between the proinflammatory immune response and antiinflammatory immune response is the pathophysiological basis for sepsis-induced immunosuppression, and epigenetic modifications regulate this balance (14). Class I histone deacetylase (HDAC1) is a histone deacetylase that typically mediates histone deacetylation on chromatin, causing the chromatin structure to condense, thereby silencing gene transcription (15, 16). In humans, HDACs are divided into 2 families on the basis of their different catalytic mechanisms: the HDAC1–11 family and the sirtuin family (17). Many studies have focused on the therapeutic efficacy of HDAC inhibitors (HDACis) in sepsis. Butyrate is a short-chain fatty acid and a potent HDACi that increases the survival rate of septic mice and reduces intestinal injury caused by sepsis (18). Valproic acid is a class I HDACi that can alleviate sepsis-induced myocardial dysfunction by accelerating autophagy (19). Although HDACis have shown promise in modulating immune responses during sepsis, the molecular link between HDAC and CD8+ T cell exhaustion in sepsis has not been established.
Here, we integrated large-scale clinical data, single-cell transcriptomics, bulk RNA-Seq, and mechanistic experiments to characterize CD8+ T cell dysfunction during sepsis. We identified HDAC1 as a key epigenetic driver of CD8+ T cell exhaustion through interaction with nuclear factor of activated T cells (NFAT1) and disruption of the transcriptional balance of activator protein-1 (AP-1) and NFAT. Pharmacological inhibition of HDAC1 restored T cell function and improved survival in sepsis models, highlighting HDAC1 as a promising therapeutic target for sepsis-induced immunosuppression.
ResultsThe percentage of peripheral blood lymphocytes, particularly the proportion of CD8+ T cells, serves as a key biomarker for the progression of sepsis. We conducted a retrospective analysis to assess the prognostic value of the peripheral blood lymphocyte percentage in patients with sepsis with concomitant pneumonia admitted for more than 7 days using the Medical Information Mart for Intensive Care IV (MIMIC-IV database) (20). We specifically focused on pneumonia-related sepsis because pulmonary infection represents the leading source of sepsis and is strongly associated with profound immune dysregulation and susceptibility to secondary infections. Restricting the cohort to this subgroup minimized heterogeneity due to different infection sites and enhanced biological relevance for subsequent lung-focused mechanistic studies. After excluding patients with cancer or autoimmune diseases, a total of 2,467 patients were included in the analysis (Figure 1A). The exposure variable was defined as the first peripheral blood lymphocyte percentage measured within 24 hours after ICU admission. The median lymphocyte percentage was 9.00% (IQR 5.30–14.00). Baseline characteristics stratified by the median value are shown in Table 1. Patients with lymphocyte percentages below the median were older (65.58 ± 16.77 vs. 61.95 ± 17.31 years, P < 0.001), had higher Sequential Organ Failure Assessment (SOFA) scores (7.41 ± 3.94 vs. 6.55 ± 3.76, P < 0.001), and experienced longer ICU stays (10.06 ± 9.64 vs. 9.14 ± 9.26 days, P = 0.016) compared with those above the median. Most notably, the lower lymphocyte percentage group exhibited substantially greater ICU mortality (31.47% vs. 15.64%, P < 0.001), whereas the sex distribution was not significantly different between the groups (P = 0.656) (Table 1). Consistent with these differences, Kaplan-Meier survival curves stratified by the prespecified median cutoff (9.00%) showed significantly lower survival in the low-lymphocyte group throughout the follow-up period, with early and persistent separation of the curves (log-rank P < 0.0001; Figure 1C). The restricted cubic spline regression adjusted for age, sex, and SOFA score revealed an L-shaped association between lymphocyte percentage and 28-day mortality; beyond 9.05%, the incremental mortality risk was substantially attenuated (Figure 1B). This nonlinear relationship underscores the clinical utility of monitoring the lymphocyte percentage as an early warning threshold for patient prognosis. Predictive performance analysis showed that lymphocyte percentage alone yielded an AUC of 0.647, comparable to SOFA (AUC = 0.652) and superior to age (AUC = 0.625). Importantly, combining lymphocyte percentage with SOFA significantly improved prediction (AUC = 0.738, P < 0.001) (Figure 1D).
Figure 1Associations between lymphocyte counts and the CD4/CD8 ratio and prognosis of patients with sepsis. (A) Flowchart showing selection of patients from MIMIC-IV database: 18,220 sepsis admissions were initially identified; after excluding patients without pneumonia (n = 11,624) and those with cancer or autoimmune diseases (n = 4,129), 2,467 patients were included in the final analysis. (B) Restricted cubic spline (RCS) for relationships between initial lymphocyte percentage after admission and 28-day ICU mortality in MIMIC-IV cohort. Solid red line is estimated ORs with 95% CI (red area); vertical dashed line is L-shaped cutoff (9.05%); solid pink curves are fraction of population with different lymphocyte percentages. P < 0.001 for overall association and nonlinearity. (C) Kaplan-Meier survival curves comparing 28-day survival between patients with sepsis with low versus high lymphocyte percentage, stratified by median value at ICU admission. Log-rank test was used to assess differences between groups (P < 0.0001). (D) ROC curves comparing predictive performance of initial lymphocyte percentage (AUC = 0.6469), SOFA score (AUC = 0.6521), and age (AUC = 0.6254) for 28-day mortality in patients with sepsis. AUC with 95% CIs is indicated. AUC comparisons were performed using DeLong’s test. (E) Representative flow cytometry contour plot showing CD4+ and CD8+ T cell subsets gated on live CD3+ lymphocytes from peripheral blood of patients with sepsis. Quadrants indicate proportions of CD4+ (upper left), CD8+ (lower right), double-negative (lower left), and double-positive (upper right) T cell populations. (F) Multivariate linear regression analysis assessing factors associated with SOFA score. Variables included CD4/CD8 ratio, CD8+ T cell proportion, CD4+ T cell proportion, and age. β coefficients with 95% CIs and P values are shown. (G) Mediation analysis illustrating indirect effect of CD8+ T cell proportion on 28-day mortality through SOFA score. Total, direct, and indirect effects (β coefficients) with corresponding P values shown. Indirect effect significance assessed using Bayesian approach (1,000 iterations).
Table 1Clinical characteristics of patients with sepsis stratified by median peripheral blood lymphocyte percentage in MIMIC cohort
To further investigate the relationships between T lymphocyte subsets and disease severity, prospective T cell data were collected from 140 patients with sepsis admitted to the ICU for more than 7 days (Supplemental Table 1; supplemental material available online with this article; https://doi.org/10.1172/jci.insight.197224DS1). Multivariable linear regression analysis revealed that the CD4+/CD8+ T cell ratio measured by flow cytometry (Figure 1E) in peripheral blood was positively associated with the SOFA score (β = 4.88, P < 0.001), whereas neither CD4+ T cell percentage, CD8+ T cell percentage, nor age exhibited significant associations after covariate adjustment (all P > 0.26) (Figure 1F). To delineate the role of T cell subsets in sepsis progression, Bayesian causal mediation analysis was performed with CD8 percentage as the exposure, SOFA score as the mediator, and ICU mortality as the outcome. CD8+ T cell percentage was significantly associated with lower SOFA scores (β = –0.310; P < 0.001), and the indirect effect of CD8+ T cell percentage on mortality via SOFA was statistically significant (β = –0.014; 95% CI: –0.024 to –0.003; P < 0.001), accounting for 82.317% of the total effect, whereas the direct effect was nonsignificant (Figure 1G and Supplemental Table 2). These findings indicate that CD8+ T cell depletion may influence clinical outcomes primarily through its contribution to organ failure severity. In contrast, mediation analysis using CD4+ T cell percentage as the exposure did not reveal significant indirect or direct effects on mortality (indirect effect β = 0.001, P = 0.306; mediation proportion 37.304%; Supplemental Table 3), suggesting that CD4+ T cell dynamics play a limited role in determining outcomes through the SOFA score. These findings underscore the prognostic relevance of CD8+ T cell dynamics in sepsis and highlight the SOFA score as a mechanistic link between immune dysregulation and clinical outcomes.
Single-cell sequencing analysis revealed a significant decrease in CD8+ T cells and an increase in the proportion of exhausted CD8+ T cells in the lungs of septic mice. Lung infections, particularly severe pneumonia, are the most common causes of sepsis, often leading to acute lung injury and acute respiratory distress syndrome. The lungs are highly susceptible to sepsis-induced damage, and respiratory failure is among the most severe complications of sepsis. Additionally, sepsis triggered by extrapulmonary factors, such as pancreatitis, systemic infections, trauma, and burns, can also result in pulmonary damage (
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