CD39 and inflammatory bowel diseases (IBD)
IBD, including Crohn’s disease and ulcerative colitis, is characterized
by chronic relapsing intestinal inflammation[130]. The expression of CD39 on endothelial cells
or immune cells integrates the dynamic balance of immunity, thereby
controlling hemostasis and immunobiological responses, which appear
disrupted in IBD [131]. Decreased abundance of
CD39-expressing intraepithelial T-cells is common in IBD patients[132]. CD39 expression by Treg was lower in active
inflammatory bowel disease and increased significantly after treatment
in responders [133]. Single nucleotide
polymorphisms (SNPs) adjacent to the CD39 promoter region have been
associated with low levels of CD39 mRNA expression which confer
susceptibility to Crohn’s disease [131]. The
number of SupTh17 cells is diminished in Crohn’s disease patients;
however, they express higher levels of CD39 and effectively generate
eAMP and ADO and, hence, can potently suppress effector T-cell responses
via A2AR [134]. In the mouse
model, changes in ADO production, such as those associated with CD39 or
CD73 gene deletions, lead to a more severe course of experimental
colitis [131, 135]. Paradoxically, Kunzli et al.[136] found that 2,4,6-trinitrobenzene sulphonic
acid colitis was attenuated in CD39-null mice, and impaired adaptive
cellular immune reactivity of CD39-null environment appears protective
in hapten-mediated Th1-type colitis.