CD39 and dendritic cells (DCs)
CD39 is expressed in both human and mouse DCs [74, 75]. Mouse bone marrow-derived DCs constitutively express CD39 but do not express CD73; thus, AMP is not converted into ADO[76]. The net effect of CD39 on the regulation of DC function may be determined by a number of factors, including the balance of P2XR and P2YR expression in specific DC populations and the concentration of local eATP, ADP, and certain nucleotides. Mizumoto et al. demonstrated that CD39 expression on dendritic cells is required for the optimal stimulation of hapten-reactive T-cells[75]. CD39 is considered necessary to prevent desensitization of the P2 receptor, which is required for the optimal function of DCs. Langerhans cells are a type of epithelial dendritic cells, which are characterized by high expression levels of CD39 and show a decrease in antigen presentation ability in the absence of CD39[75]. CD39-/- mice have major defects in dendritic cell formation, antigen presentation, and response to semi-antigens [77]. Dwyer et al. proposed that the functional defect of CD39-/- dendritic cells is due to its impaired ability to initiate and maintain cell-cell contact, and that CD39 might be transferred to immune synapses to facilitate cell contact signals during antigen presentation [52]. On the contrary, Yoshida et al. showed that CD39-deficient hepatic dendritic cells exhibit more mature phenotypes, stronger responsiveness to TLR ligands, and stronger pro-inflammatory and immunostimulatory activities [78]. IL-27 can up-regulate CD39 on the surface of DC and then reducing the concentration of ATP and the activation of NLRP3 inflammatory bodies, thus limiting the differentiation of Th1 and Th17 cells and promoting immune tolerance[79]. LPS can down-regulated membrane CD39 expression via endocytosis in bone marrow-derived dendritic cells (BMDCs), which was positively associated with decreased enzymatic activity in ATP metabolism and increased eATP accumulation, leading to the activation of P2X7R, which mediated a pro-inflammatory effect[80].