Trauma Induces Interleukin-17A Expression on Th17 Cells and CD4+ Regulatory T Cells as Well as Platelet Dysfunction

Abstract

Background: The organism's immune response to trauma is distinctively controlled, its dysregulation leading to severe post-traumatic complications. Platelets, CD4+ regulatory T cells (CD4+ Tregs) and T helper 17 (Th17) cells have been identified to participate in the post-traumatic immune response. Unfortunately, little is known about their exact role and potential interdependency in humans. Aims of this clinical trial were to phenotype the human immune response following injury and to identify risk factors rendering the host more susceptible to trauma induced injury.Methods: This non-interventional prospective clinical trial enrolled patients following multiple trauma, follow up was conducted for 10 days. Peripheral blood CD4+ Tregs and Th17 cells were analyzed using flow cytometry to determine Interleukin 17A (IL-17A) expression. Hemostasis and platelet function were assessed with rotational thromboelastometry (ROTEM®). Subgroup analysis was conducted for the factors gender, age, and trauma severity.Results and Conclusion: This is the first clinical trial to phenotype the immune response following trauma, focusing on platelets, and the adaptive immune response. We discovered a novel increased IL-17A expression on Th17 cells and on CD4+ Tregs following trauma and describe the kinetics of the immune response. The IL-17A response on CD4+ Tregs challenges the ascribed role of CD4+ Tregs to be solely counter inflammatory in this setting. Furthermore, despite a rising number of platelets, ROTEM analysis shows post-traumatic platelet dysfunction. Subgroup analysis revealed gender, age, and trauma severity as influencing factors for several of the analyzed parameters.

The potential of adipokines in identifying multiple trauma patients at risk of developing multiple organ dysfunction syndrome

“…The multiple trauma patients showed statistically significant higher interleukin-17A plasma concentrations throughout the observation period, as compared to the control group. This is in line with the work of Abboud [49]. In this study, the multiple trauma patients with MOF showed statistically significant higher IL-17A concentrations at the time points 0 h, 48 h and 72 h, as compared to the trauma patients without MOF.…”

The Potential of Adipokines in Identifying Multiple Trauma Patients at Risk of Developing Multiple Organ Dysfunction Syndrome

“…This is in line with the work of Abboud et al, who highlighted the importance of IL-17A in the post-traumatic immune response in patients with a severe blunt trauma [46]. Furthermore, Hefele et al discovered an increased IL-17A expression on TH-17 cells and CD4 + Tregs following trauma [47]. In this study, the multiple trauma patients with MOF showed statistically signi cantly higher IL-17A concentrations at the time points 0 h, 48 h and 72 h, as compared to the trauma patients without MOF.…”

Dysregulated TP53 Among PTSD Patients Leads to Downregulation of miRNA let-7a and Promotes an Inflammatory Th17 Phenotype

“…NK/NKT cells are also lowly expressed in PBMCs compared to T helper cell subsets (62), and in addition, NK cells do not normally express T cell-associated CD3. Collectively, these observations strongly suggest the source of increased IL-17A in PTSD patients is most likely derived from CD4+ Th17 cells, which is supported by a report from Hefele et al which showed trauma can increase IL-17A specifically in Th17 subsets (63).…”

“…Collectively, these observations strongly suggest the source of increased IL-17A in PTSD patients is most likely derived from CD4+ Th17 cells, which is supported by a report from Hefele et al. which showed trauma can increase IL-17A specifically in Th17 subsets ( 63 ).…”