Neuropilin-1highCD4?CD25? Regulatory T Cells Exhibit Primary Negative
Immunoregulation in Sepsis
#MMPMID27239104
Gao YL
; Chai YF
; Qi AL
; Yao Y
; Liu YC
; Dong N
; Wang LJ
; Yao YM
Mediators Inflamm
2016[]; 2016
(?): 7132158
PMID27239104
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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-1(high)CD4(+)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-1(high)Tregs and
Nrp-1(low)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-?
(TGF-?(m+)), apoptotic rate, and secretive ability [including TGF-? 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-?(m+) of Nrp-1(high)Tregs were upregulated
by septic challenge. Nrp-1(high)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. Nrp-1(high)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.
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