Abstract
Traumatic brain injury (TBI) can alter various immune functions, including immunosuppression, and constitutes a risk factor for nosocomial infections and organ dysfunction. Although TBI can induce a decline in immune cell function, the detailed mechanisms remains to be elucidated. We aim to explore transcriptional signatures associated with post-TBI immune alterations in a pilot cohort using a comprehensive transcriptome analysis of immune cells. Three patients with traumatic brain injury and acute subdural hematoma were admitted to our hospital. We focused on three major subsets of immune cells responsible for the immune response: CD4 + T cells, CD8 + T cells, and monocytes. We evaluated the changes in immune function after injury using comprehensive transcriptome analysis. Blood samples were collected immediately after admission and one week later, and the data were compared with those of healthy volunteers. CD4 + , CD8 + T cells, and monocytes, the expression of pathways involved in cellular metabolism—including oxidative phosphorylation, mTORC1 signaling, MYC targets V1 and V2, and the unfolded protein response—was downregulated on day 7 compared with day 1. These findings suggest a transition from marked immune activation and metabolic upregulation on day 1 to an attenuated immune response by day 7. In CD4 + T cells, pathways associated with tissue remodeling and repair, such as hedgehog signaling and epithelial–mesenchymal transition, were upregulated from days 1 to 7, indicating a shift from inflammatory responses toward inflammation resolution and tissue repair. In this pilot study, comprehensive transcriptome profiling suggests time-dependent transcriptional shifts in CD4⁺ T cells, CD8⁺ T cells, and monocytes after TBI. These findings should be interpreted as hypothesis-generating and provide a framework for larger, confirmatory studies.
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Data availability
All data generated or analyzed during this study are included in this published article. The raw data from this study were submitted to the Gene Expression Omnibus under accession numbers GSE285385 and GSE314947.
Abbreviations
- AIS-98:
-
Abbreviated injury scale 98
- CARS:
-
Compensatory anti-inflammatory response syndrome
- GCS:
-
Glasgow coma scale
- GOS:
-
Glasgow outcome scale
- HLA:
-
Human leukocyte antigen
- IQR:
-
Interquartile range
- ISS:
-
Injury severity score
- PBMC:
-
Peripheral blood mononuclear cell
- SIRS:
-
Systemic inflammatory response syndrome
- TBI:
-
Traumatic brain injury
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Acknowledgements
We thank the Department of Medical Informatics, Osaka University Hospital, Osaka, Japan, for their cooperation in the collection of data from medical records. We also thank the medical staff who participated in this study.
Funding
This study was supported by the General Insurance Association of Japan (grant to HI 2021), a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (24K12153) to HI, and a Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science (23K27701) to HO.
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HI, MI, HM, HO, and DO were involved in the conception and design of the study. HI performed the literature review. HI and MI acquired the data and performed the analysis and interpretation. HI drafted the manuscript. HI, MI, HM, HO, and DO were involved in the critical revision of the manuscript. All authors contributed to the discussions, managed the study, and read and approved the final version of the manuscript.
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The study protocol was approved by the Institutional Review Board of the University of Osaka hospital (Approval Number: 885) and complied with the principles of the Declaration of Helsinki. Written informed consent for the collection of blood samples and the use of clinical data was obtained from the patients or their relatives, and from healthy volunteers.
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Ito, H., Ishikawa, M., Matsumoto, H. et al. Gene expression changes in lymphocytes and monocytes from patients with traumatic brain injury. Sci Rep (2026). https://doi.org/10.1038/s41598-026-39991-6
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DOI: https://doi.org/10.1038/s41598-026-39991-6
