CD73‐generated adenosine regulation of colonic epithelial barrier permeability during inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal (GI) tract that is characterized by weight loss, bloody diarrhea, and increased activated immune cell infiltration in the GI tract. Since extracellular adenosine signaling has been shown to modulate inflammation during IBD, we wanted to determine if CD73, the cell surface enzyme that catalyzes the dephosphorylation of extracellular AMP to adenosine, also has a role in IBD. Therefore, we induced IBD with dextran sodium sulfate (DSS) in drinking water in cd.73−/− and wild type mice. As expected, cd73−/−mice exhibited dramatically more severe IBD than wild type mice (based on weight loss and histology). However, in attempting to verify that T cells were responsible for mediating this severe IBD (by adoptively transferring naïve CD45RBHi T cells from wild type or cd73−/− mice into RAG‐1−/− recipients, which has been proven to induce passive IBD), surprisingly, we did not see any difference between the IBD severity in mice that received wild type or cd73−/− derived cells. These results suggest that other factors (besides T cells) are regulated by CD73/adenosine during IBD. Furthermore, our data indicates that CD73 generated adenosine is involved in the regulation of colonic epithelial barrier permeability, as decreased expression of junctional adhesion molecules (JAMs) is observed in cd.73−/− DSS‐treated mice. AI 57854 (MSB)