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已发表论文
基于 GEO 公共数据库和多组学数据的整合分析：PD-L1 作为脓毒症期间 M1 型巨噬细胞中 NF-κB 通路激活潜在诱导因子
Authors Yuan M , Jin T, Zhao Q, Tian L
Received 7 November 2025
Accepted for publication 3 January 2026
Published 9 January 2026 Volume 2026:19 578828
DOI https://doi.org/10.2147/JIR.S578828
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Xin Du
Mu Yuan,* Tong Jin,* Qing Zhao, Lixing Tian
Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Lixing Tian, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Yuzhong District, Chongqing, 400042, People’s Republic of China, Tel +8618584566173, Email tianlixing@tmmu.edu.cn
Background: M1-type macrophages are a crucial defense line against pathogens during sepsis, and their polarization depends on NF-κB pathway activation. However, the specific molecular regulatory mechanisms of this process are not fully elucidated. Programmed death-ligand 1 (PD-L1), an important immune checkpoint molecule, is often anchored on the cell membrane exerting immunosuppressive effects, but its role in M1-type macrophages remains poorly understood.
Methods: In this study, we preliminarily investigated the potential regulatory effect of PD-L1 on the NF-κB pathway in M1 macrophages by integrating GEO sepsis patient sequencing datasets, RNA-seq data from PD-L1-overexpressing M1 macrophages, immunoprecipitation-mass spectrometry (IP-MS), molecular docking, and co-immunoprecipitation (Co-IP). The Receiver Operating Characteristic (ROC) curve of PD-L1 was used as a prognostic indicator for sepsis. PD-L1 knockout mice were utilized to validate the in vivo regulatory effects of PD-L1.
Results: Analysis of GEO data and peripheral blood mononuclear cells (PBMCs) from sepsis patients revealed significantly elevated PD-L1 expression with a central position among all upregulated genes. Furthermore, this elevated PD-L1 expression was validated in peripheral monocytes from sepsis patients compared to healthy controls. Single-gene GSEA analysis based on GEO data indicated a close association between PD-L1 and NF-κB pathway activation in sepsis patients. RNA-seq analysis of PD-L1-overexpressing M1 macrophages confirmed that PD-L1 significantly activates the NF-κB pathway. IP-MS screening and Co-IP validation identified an interaction between PD-L1 and KLF6, a nuclear factor closely related to the NF-κB pathway. Finally, liver transcriptome data from septic mice confirmed that PD-L1 can also activate the NF-κB pathway in vivo, and ROC curve analysis demonstrated PD-L1’s potential as a prognostic indicator for sepsis.
Conclusion: Based on these results, this study preliminarily reveals a potential activating role of PD-L1 on the NF-κB pathway in M1 macrophages.
Keywords: macrophage, NF-κB signaling pathway, PD-L1
Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Lixing Tian, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Yuzhong District, Chongqing, 400042, People’s Republic of China, Tel +8618584566173, Email tianlixing@tmmu.edu.cn
Background: M1-type macrophages are a crucial defense line against pathogens during sepsis, and their polarization depends on NF-κB pathway activation. However, the specific molecular regulatory mechanisms of this process are not fully elucidated. Programmed death-ligand 1 (PD-L1), an important immune checkpoint molecule, is often anchored on the cell membrane exerting immunosuppressive effects, but its role in M1-type macrophages remains poorly understood.
Methods: In this study, we preliminarily investigated the potential regulatory effect of PD-L1 on the NF-κB pathway in M1 macrophages by integrating GEO sepsis patient sequencing datasets, RNA-seq data from PD-L1-overexpressing M1 macrophages, immunoprecipitation-mass spectrometry (IP-MS), molecular docking, and co-immunoprecipitation (Co-IP). The Receiver Operating Characteristic (ROC) curve of PD-L1 was used as a prognostic indicator for sepsis. PD-L1 knockout mice were utilized to validate the in vivo regulatory effects of PD-L1.
Results: Analysis of GEO data and peripheral blood mononuclear cells (PBMCs) from sepsis patients revealed significantly elevated PD-L1 expression with a central position among all upregulated genes. Furthermore, this elevated PD-L1 expression was validated in peripheral monocytes from sepsis patients compared to healthy controls. Single-gene GSEA analysis based on GEO data indicated a close association between PD-L1 and NF-κB pathway activation in sepsis patients. RNA-seq analysis of PD-L1-overexpressing M1 macrophages confirmed that PD-L1 significantly activates the NF-κB pathway. IP-MS screening and Co-IP validation identified an interaction between PD-L1 and KLF6, a nuclear factor closely related to the NF-κB pathway. Finally, liver transcriptome data from septic mice confirmed that PD-L1 can also activate the NF-κB pathway in vivo, and ROC curve analysis demonstrated PD-L1’s potential as a prognostic indicator for sepsis.
Conclusion: Based on these results, this study preliminarily reveals a potential activating role of PD-L1 on the NF-κB pathway in M1 macrophages.
Keywords: macrophage, NF-κB signaling pathway, PD-L1