Abstract
Sepsis-induced acute lung injury (ALI) is a critical clinical condition characterized by severe inflammation and alveolar epithelial barrier disruption, with limited effective treatments. Our study investigates the role of Sbno2-expressing tissue-resident alveolar macrophages (TR-AMs) in promoting alveolar epithelial cell (AEC) regeneration and barrier function in sepsis-induced ALI. Utilizing single-cell RNA sequencing (scRNA-seq), we identified significant upregulation of Sbno2 in TR-AMs, which correlated with enhanced AEC proliferation and reduced apoptosis. Functional assays demonstrated that Sbno2-expressing TR-AMs substantially supported alveolar structure regeneration in both in vitro and in vivo models. Knockout of Sbno2 in TR-AMs impaired AEC proliferation and compromised lung barrier integrity. Therapeutic administration of recombinant Sbno2 (rSbno2) in a sepsis-induced ALI mouse model alleviated lung injury, promoted AEC proliferation, and restored barrier function, highlighting Sbno2 as a potential therapeutic target for ALI. These findings provide novel insights into the molecular mechanisms of lung repair in sepsis-induced ALI and suggest that enhancing Sbno2 expression in TR-AMs could be a promising strategy for improving outcomes in patients with ALI.
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Funding
This study was supported by 2024 Guangdong Provincial Basic and Applied Basic Research Fund Natural Science Foundation Project-General project (Project ID: 2024A1515010633), Guangdong Province Hospital Association Pharmaceutical Research Fund, Medical Clinical Research of Charity and Public Welfare undertakings (Project No.: 2022YXKY01).
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Dai J.Y. and Wu Z.H. conceived and designed the study. Zhong J.Y., Wu X.L., and Liu Y.B. performed the experiments. Yang Q. and Zhang L.L. analyzed the data. Zhong J.Y. and Zhang S.Y. wrote the manuscript. All authors reviewed and approved the final version of the manuscript.
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All animal experiments were conducted in strict accordance with the guidelines of the Institutional Animal Care and Use Committee, and the study was approved by the Animal Ethics Committee of Guangzhou Red Cross Hospital of Jinan University with the approval number No. 2023-123-01. The study did not involve any clinical ethics as it was preclinical in nature.
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Dai, J., Wu, Z., Zhong, J. et al. Sbno2-mediated tissue-resident alveolar macrophages: a novel therapeutic axis for sepsis-induced acute lung injury. Cell Death Discov. (2026). https://doi.org/10.1038/s41420-025-02772-7
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DOI: https://doi.org/10.1038/s41420-025-02772-7
