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].