Abstract
Regulatory T cells (Tregs) appear to be involved in sepsis-induced immune dysfunction; neuropilin-1 (Nrp-1) was identified as a surface marker for CD4+CD25+Tregs. In the current study, we investigated the negative immunoregulation of Nrp-1highCD4+CD25+Tregs and the potential therapeutic value of Nrp-1 in sepsis. Splenic CD4+CD25+Tregs from cecal ligation and puncture (CLP) mouse models were further segregated into Nrp-1highTregs and Nrp-1lowTregs; they were cocultured with CD4+CD25− T cells. The expression of forkhead/winged helix transcription factor-3 (Foxp-3), cytotoxic T-lymphocyte associated antigen-4 (CTLA-4), membrane associated transforming growth factor-β (TGF-βm+), apoptotic rate, and secretive ability [including TGF-β and interleukin-10 (IL-10)] for various types of Tregs, as well as the immunosuppressive ability of Tregs on CD4+CD25− T cells, were determined. Meanwhile, the impact of recombinant Nrp-1 polyclonal antibody on the demethylation of Foxp-3-TSDR (Treg-specific demethylated region) was measured in in vitro study. Sepsis per se markedly promoted the expression of Nrp-1 of CD4+CD25+Tregs. Foxp-3/CTLA-4/TGF-βm+ of Nrp-1highTregs were upregulated by septic challenge. Nrp-1highTregs showed strong resilience to apoptosis and secretive ability and the strongest immunosuppressive ability on CD4+CD25− T cells. In the presence of lipopolysaccharide (LPS), the recombinant Nrp-1 polyclonal antibody reduced the demethylation of Foxp-3-TSDR. Nrp-1highTregs might reveal primary negative immunoregulation in sepsis; Nrp-1 could represent a new potential therapeutic target for the study of immune regulation in sepsis.
Highlights
Sepsis is still a leading cause of death among critical patients in the intensive care units, and the life quality of the survivors would usually be impaired [1,2,3,4,5]
Investigahelper T cell 1 (Th1) to Th2 response, especially immunoparalysis via expression of cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and TGF-βm+, as well as antitors have become interested in the study of the mecha- inflammatory cytokines (IL-10 and TGF-β) [12,13,14,15,16,17]
E The secretion of IFN-γ and IL-10 from CD4+ CD25− T cells when cocultured with Tregs for 24 hrs Control LPS 1 μg/mL 10 μg/mL 100 μg/mL 1000 μg/mL 10000 μg/mL
Summary
Sepsis is still a leading cause of death among critical patients in the intensive care units, and the life quality of the survivors would usually be impaired [1,2,3,4,5]. Rof immunocytes, including B/T-lymphocytes, dendritic cells (DCs), gastrointestinal epithelial cells, and even thymocytes, including both activation of Tregs and apoptotic depletion of immunocytes [10]. During the development of sepsis, Tregs subdue inflammation and tissue damage, and at the beginning of sepsis as shown in both animal models and septic patients [6,7,8,9]. It has been noted that the septic they may cause immune dysfunction, such as induction of T-lymphocytic apoptosis, inhibition of CD4+/CD8+ T-. Patients would gradually enter immunosuppression after lymphocytic function, and mediation of shifting from the primary hyperinflammatory response, which is defined as immunoparalysis [2, 4, 6, 7]. Investigahelper T cell 1 (Th1) to Th2 response, especially immunoparalysis via expression of CTLA-4 and TGF-βm+, as well as antitors have become interested in the study of the mecha- inflammatory cytokines (IL-10 and TGF-β) [12,13,14,15,16,17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
