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].