CD39 and sepsis
Sepsis is caused by an imbalance in the host immune response to
infection, and it can lead to life-threatening organ dysfunction. CD39
attenuates sepsis-associated liver injury by scavenging eATP and
ultimately generating ADO. Boosting of CD39 can suppress P2X7R response
and trigger adenosinergic signaling to limit systemic inflammation and
restore liver homeostasis during the acute phase of sepsis[87]. CD39 enhancement also exhibited an enhancing
effect on the ability of renal tubular epithelial cells to resist
LPS-induced damage, improve cell viability and apoptosis, and inhibit
NLRP3 inflammasome activation [123]. Increase
CD39+ Tregs was associated with a poor prognosis for
sepsis patients, which suggests that the CD39+ Treg
level is a potential biomarker for predicting the outcome of sepsis in
patients [124]. CD39 affects the pro-inflammatory
response of sepsis mediated by immune cells and endothelial cells. Cohen
et al. showed that TLR-stimulated macrophages modulate their activation
state by increasing the synthesis and secretion of ATP[86]. Macrophages lacking CD39 are unable to
transition to a regulatory state and consequently continue to produce
inflammatory cytokines. Furthermore, the macrophage-specific expression
of CD39 is critical for preventing lethal hyperinflammatory responses to
LPS in vivo [86] . Overexpression of CD39 in
the endothelium efficiently abrogated the initial phases of ATP
secretion in response to LPS endotoxin and markedly inhibited IL-1α
release [125]. CD39 expression is up-regulated
during sepsis [126, 127]. Bao et al. indicate that
ADO, the ADO A2AR agonist, E2F-1, and CREB are potential
factors contributing to the increased expression of CD39 and CD73 on
Treg cell surface during sepsis [128]. It was
reported miR-155 induces an increased percentage of
CD39+ Tregs and thus immunosuppression in sepsis
patients [129].