adora2b adenosine receptor engagement enhances regulatory t cell abundance during endotoxin-induced pulmonary inflammationadora2b腺苷受体参与有助于提高调节性t细胞丰度在endotoxin-induced肺部炎症.pdfVIP

Adora2b Adenosine Receptor Engagement Enhances Regulatory T Cell Abundance during Endotoxin-Induced Pulmonary Inflammation . . Heidi Ehrentraut , Joseph A. Westrich , Holger K. Eltzschig, Eric T. Clambey* Mucosal Inflammation Program, Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado, United States of America Abstract Anti-inflammatory signals play an essential role in constraining the magnitude of an inflammatory response. Extracellular adenosine is a critical tissue-protective factor, limiting the extent of inflammation. Given the potent anti-inflammatory effects of extracellular adenosine, we sought to investigate how extracellular adenosine regulates T cell activation and differentiation. Adenosine receptor activation by a pan adenosine-receptor agonist enhanced the abundance of murine ¨ regulatory T cells (Tregs), a cell type critical in constraining inflammation. Gene expression studies in both naıve CD4 T cells and Tregs revealed that these cells expressed multiple adenosine receptors. Based on recent studies implicating the Adora2b in endogenous anti-inflammatory responses during acute inflammation, we used a pharmacologic approach to specifically activate Adora2b. Indeed, these studies revealed robust enhancement of Treg differentiation in wild-type mice, but not in Adora2b 2/ 2 T cells. Finally, when we subjected Adora2b-deficient mice to endotoxin-induced pulmonary inflammation, we found that these mice experienced more severe inflammation, characterized by increased cell recruitment and increased fluid leakage into the airways. Notably, Adora2