Neuropilin-1highCD4+CD25+ Regulatory T Cells Exhibit Primary Negative Immunoregulation in Sepsis

Abstract EN

Regulatory T cells (Tregs) appear to be involved in sepsis-induced immune dysfunction; neuropilin-1 (Nrp-1) was identified as a surface marker for C D 4 + C D 25 + Tregs.

In the current study, we investigated the negative immunoregulation of N r p - 1 h i g h C D 4 + C D 25 + Tregs and the potential therapeutic value of Nrp-1 in sepsis.

Splenic C D 4 + C D 25 + Tregs from cecal ligation and puncture (CLP) mouse models were further segregated into N r p - 1 h i g h Tregs and N r p - 1 l o w Tregs; 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- β m + ), 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 C D 4 + C D 25 + Tregs.

Foxp-3/CTLA-4/TGF- β m + of N r p - 1 h i g h Tregs were upregulated by septic challenge.

N r p - 1 h i g h Tregs 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.

N r p - 1 h i g h Tregs might reveal primary negative immunoregulation in sepsis; Nrp-1 could represent a new potential therapeutic target for the study of immune regulation in sepsis.