CD73 Is Critical for the Resolution of Murine Colonic Inflammation

الملخص EN

CD73 is a glycosyl-phosphatidylinositol-(GPI-) linked membrane protein that catalyzes the extracellular dephosphorylation of adenosine monophosphate (AMP) to adenosine.

Adenosine is a negative regulator of inflammation and prevents excessive cellular damage.

We investigated the role of extracellular adenosine in the intestinal mucosa during the development of Dextran-Sulfate-Sodium-(DSS-)salt-induced colitis in mice that lack CD73 (CD73−/−) and are unable to synthesize extracellular adenosine.

We have found that, compared to wild-type (WT) mice, CD73−/− mice are highly susceptible to DSS-induced colitis.

CD73−/− mice exhibit pronounced weight loss, slower weight recovery, an increase in gut permeability, a decrease in expression of tight junctional adhesion molecules, as well as unresolved inflammation following the removal of DSS.

Moreover, colonic epithelia in CD73−/− mice exhibited increased TLR9 expression, high levels of IL-1β and TNF-α, and constitutive activation of NF-κB.

We conclude that CD73 expression in the colon is critical for regulating the magnitude and the resolution of colonic immune responses.