Gene expression changes in lymphocytes and monocytes from patients with traumatic brain injury: A prospective case-control study

Background: 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. This study aimed to characterize the mechanism of immunosuppression caused by TBI using a comprehensive transcriptome analysis of immune cells. Methods: 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. Results: 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 (EMT), were upregulated from day 1 to day 7, indicating a shift from inflammatory responses toward inflammation resolution and tissue repair. Conclusions: Comprehensive transcriptome analysis might suggest impaired immune responses and pathway in CD4+ T cells, CD8+ T cells, and monocytes. This study contributes to the further elucidation of the mechanisms of immunosuppression due to traumatic brain injury. Overall design: We performed a retrospective, observational, case-control, single-center study. Samples from the patients were collected at two timepoints: within 24 h of admission and on the 7th or 8th day of admission. PBMCs were isolated from fresh whole blood. Two panels were used to identify subsets of CD4+ T cells, CD8+ T cells, and monocytes from PBMCs. Total RNA was extracted from the sorted cells. Whole-transcriptome sequencing was performed on an Illumina NovaSeq 6000 platform using a pair-end sequencing strategy.