Gene expression changes related to immunosuppression in patients with traumatic brain injury (Part 2)

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 remain unclarified. This study aimed to clarify the mechanism of immunosuppression caused by TBI using a comprehensive transcriptome analysis of immune cells. Methods : Six 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+ T cells and CD8+ T cells decreased over seven days following injury, and a decrease in cell adhesion and endoplasmic reticulum function was observed. It was suggested that the process of protein synthesis from RNA was impaired and that overall cell function was reduced. Monocytes also show a decrease in endoplasmic reticulum function, but classical and nonclassical monocyte subsets show an increase in functions related to platelet activation and tissue repair. Conclusions : Comprehensive transcriptome analysis confirmed a decrease in endoplasmic reticulum function in CD4+ T cells, CD8+ T cells, and monocytes. This study facilitates further elucidation of the mechanisms of immunosuppression due to trauma and the development of new therapeutic strategies to suppress secondary infections. 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 151-base pair-end sequencing strategy.