Research Of Imbalance Of Th17/CD4~+CD25~+Foxp3~+ Regulatory T Cell In Posttraumatic Sepsis

Objective:To investigate the imbalance between Th17 cell and CD4+CD25+Foxp3+ regulatory T cell (Treg), the expression of related cytokines and the possible mechanism during posttraumatic sepsis process. To further explore the pathogenesis of disturbed adaptive immune response during posttraumatic sepsis.Methods:clinical reseach:35 cases of severe traumatic patients (13 cases with posttraumatic sepsis while 22 cases without) and 9 cases of healthy volunteers were enrolled in this study. The main research contents include separating peripheral blood lymphocyte to detect the percentage of Th17 cell and Treg cell by Flow, the expression of RORyt mRNA and Foxp3 mRNA by qPCR, at the same time the related cytokines in serum such as CRP, IL-4, IL-6,IL-10, IL-17, IL-23,INF-γ, TGF-βwere tested by ELISA and all the data were analysed combined with the clinical data.Animal experiment:52 cases of male Balb/c were separate into control group (4 cases), sham group(16 cases), CLP group(16 cases) and RU group(16 cases) randomly and underwent relevant treatments. Investigated the percentage of Th17 cell and Treg cell, the expression of RORγt mRNA and Foxp3 mRNA in spleen, and the related cytokines in serum such as IL-2,IL-4, IL-6, IL-10, IL-17, INF-γand TGF-β. Meanwhile, the DTH reaction was measured to evaluate the T cell response.Results:clinical reseach:The hospital stay and case fatality rate in sepsis group is higher than those in trauma group (P<0.05).The proportion of Th17 cells and mRNA expression of transcription factor RORyt in sepsis group was found to be significantly higher than that in healthy control or trauma group (P<0.01). The proportion of Treg cells and the mRNA expression of the transcription factor Foxp3 were significantly increased in sepsis group and trauma group (P<0.05). while there is no significant difierence between these two groups (P>0.05). Serum levels of Thl7 inducing cytokine such as IL-6, IL-23 and IL-17 were significantly elevated in sepsis group than that in trauma group or healthy control group(P<0.05), while cytokine such as TGF-βand IL-10 were found higher in sepsis and trauma group than that in healthy control group (P<0.01). Serum levels of CRP and IL-4 in trauma group and sepsis group was higher(P<0.05) than those in control group while levels of INF-γwas lower (P<0.05). Animal experiment:Proportion of Thl7 cell in CLP group, RU group and sham group was found increased from the fitst day compared with control group (P<0.01), then CLP and RU group continued to increase to day 3, then decreased, the difference between these two group was not significant (P>0.05), while the mRNA expression of transcription factor RORγt and the serum levels of Th17 inducing cytokine such as IL-6, IL-17 had a similar variation tendency. Proportion of Treg cell in CLP and RU group was found in a sustainable growth with a only a slightly reduction in the 3rd day. Between these two groups, the proportion of Treg cell was higher in CLP group (P< 0.05). the mRNA expression of Treg cell transcription factor Foxp3 and the serum levels of Treg cell related cytokines such as TGF-P, IL-2, IL-10 had a similar variation tendency. Serum levels of INF-y and IL-4 were found no significant difference among all groups. The DTH test showed that the response of mice in sham group and control group has no significant difference, while RU group and CLP group had significant lower response (P<0.01). between these two group, the CLP group had the lower response (P<0.05).Conclusion:Th17 cells involve in the inflammation during posttraumatic sepsis. Treg cells play an anti-inflammatory role during posttraumatic sepsis and maintain a deferment immunosuppression state. Th17/Treg imbalance occurs after sepsis, is the important mechanism of immune disorders. GC/GR participation may cause Thl7/Treg cell imbalance during posttraumatic sepsis. Moderate antagonist glucocorticoids function may in some extent reverse imbalance of Thl7/Treg cell, and reverse excessive deferment immunosuppression. Those may contribute to the state of the original infection status thoroughly clearance and prevent the occurrence of secondary infection, improve the prognosis.