CD39 and ischemia-reperfusion injury (IRI)
In CD39 and CD73 knockout mice, organ damage and inflammation caused by ischemia in the brain [84], heart[137-139], kidney [140, 141], liver [142, 143], intestine[144, 145] and hindlimb[146] were more severe than those in the corresponding wild-type mice. Studies have shown that boosting of CD39 can reduce organ damage caused by IR [147-150]. The protective effect observed in CD39 over-expressing mice on myocardial ischemia has been shown to work through the A2BR dependence mechanism [151]. This protective effect was also observed in pigs over-expressing CD39[152]. A variety of immune cells are involved in the protective effect of CD39 on IRI. In vitro activated Tregs ameliorated IRI through a CD39-dependent mechanism[153]. In addition, deletion of CD39 in NK cells inhibits their activation and protects partial hepatic IRI by diminishing IFN-γ production [67].IRI is inherent in organ transplantation and has an impact on both short-term and long-term outcomes of the transplantation. CD39 expression in mouse liver conventional myeloid DCs (mDCs) limits the pro-inflammatory activity of mDCs and provides protection against the innate immune response against liver transplant IRI [78]. Furthermore, liver grafts from CD39-over-expressing mice have been shown to be protected from IRI due to the reduced numbers of resident CD4+ T-cells [154]. The expression of CD39 can be up-regulated by hypoxia and specificity protein 1 (Sp1)-mediated induction of cardiac CD39 during myocardial ischemia [24].