BackgroundSepsis is a life‐threatening disease that is an immune disorder response that causes multiple organ dysfunction. In this study, we investigated the dynamic changes in mRNA expression of HLA‐DRA gene and the specific transcription factor of helper T cell subsets to explore long‐term immunophenotyping and its relationship with prognosis.MethodsSeventy‐eight sepsis patients and twelve healthy controls were recruited in this study. Blood samples were collected at eight‐time points during their septic course and were assayed for the gene expression of HLA‐DRA and T helper cell subset‐specific transcription factors (T‐bet: Th1, GATA3: Th2, Foxp3: Treg, RORC: Th17).ResultsThe levels of HLA‐DRA in survivors gradually increased but were maintained at lower levels in non‐survivors. The specific transcription factor of Th1 and Th2 cells, T‐bet and GATA‐3 were significantly lower in sepsis patients than in normal controls, and the non‐survivors showed significantly lower levels than the survivors (P < .05). RORC and FOXP3, the specific transcription factor of Treg and Th17 were significantly higher in survivors than in non‐survivors and normal controls (P < .05). T‐bet and GATA‐3 had a linear correlation with HLA‐DRA expression (P < .01).ConclusionsThe dynamic changes in HLA‐DRA expression in peripheral blood could accurately reflect the immune status of sepsis patients, and the reduction in HLA‐DRA may be an important reason for abnormal T cell differentiation. The sustained low levels of the Th cell subsets (Th1 and Th2) suggest the suppression of adaptive immunity, and this persistent immunosuppression may be the leading cause of death in septic patients.
Lymphocyte apoptosis appears to play an important role in immunodysfunction in sepsis. We investigated the role of miR-223 in cell proliferation and apoptosis to identify potential target downstream proteins in sepsis. We recruited 143 patients with sepsis and 44 healthy controls from the Chinese PLA General Hospital. Flow cytometry was used to sort monocytes, lymphocytes, and neutrophils from fresh peripheral blood. A miR-223 mimic and inhibitor were used for transient transfection of Jurkat T cells. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to assess expression of the miRNAs in cells. Western blot analysis was performed to measure protein expression. We evaluated the cell cycle and apoptosis by using flow cytometry (FCM) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Expression of miR-223 was significantly higher in the survivor group than in the nonsurvivor group. Multiple linear regression analysis revealed that SOFA scores correlated negatively with miR-223 and monocyte counts, with β coefficients (95% CI) of − 0.048 (− 0.077, − 0.019) and − 47.707 (− 83.871, − 11.543), respectively. miR-223 expression also correlated negatively with the percentage of apoptosis in lymphocytes. The rate of apoptosis in the miR-223 mimic group was significantly lower than that of the negative control, with an adverse outcome observed in the miR-223 inhibitor group. We also found that miR-223 enhanced the proliferation of Jurkat T cells and that inhibiting miR-223 had an inhibitory effect on the G1/S transition. We conclude that miR-223 can serve as a protective factor in sepsis by reducing apoptosis and enhancing cell proliferation in lymphocytes by interacting with FOXO1. Potential downstream molecules are HSP60, HSP70, and HTRA.
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